Journal of Respiration doi: 10.3390/jor6020009

Authors: Quevedo Rodríguez Rodríguez Salvador Domínguez Zamora Ros Viejo

Background/Objectives: COPD instability is heterogeneous; GOLD 2026 lowers the prior-year threshold to ≥1 moderate or severe exacerbation. We assessed whether this low-threshold criterion behaves as a high-sensitivity operational signal in primary-care EHRs. Methods: A retrospective multicenter same-window EHR pilot study in two Spanish primary-care centers (n = 106). Predictors and six binary endpoints were aggregated over the same 12-month window: any exacerbation, high-risk history, severe hospitalization, SABA dispensing, SAMA dispensing, and any rescue dispensing. We fitted Bayesian multi-outcome hierarchical logistic models with patient-level random intercepts, cross-endpoint partial pooling, regularizing priors, and missingness indicators. Robustness used prespecified scenarios, 10-fold ELPD cross-validation, and high-missingness exclusion. Results: Any exacerbation occurred in 53/106 patients; high-risk history in 25/106; hospitalization in 16/106; and any rescue dispensing in 65/106. Diagnostics were stable, and posterior predictive checks supported marginal adequacy. Heart failure showed the clearest positive pattern across exacerbation-defined endpoints; reliever-dispensing endpoints showed a distinct care-pathway-sensitive pattern. No scenario improved out-of-sample adequacy. High-missingness exclusion preserved directionality in 120/120 overlapping pairs; the median |ΔlogOR| was 0.061; and 119/120 remained within ±log(1.25). Conclusions: GOLD 2026 “any exacerbation” behaved as a high-sensitivity operational signal in an endpoint-operating-point sense, not as a homogeneous phenotype. Findings are within-window associations, not causal, medication-effect, or prospective prediction estimates; external validation is required.

Journal of Respiration doi: 10.3390/jor6020008

Authors: Santiago Serna Marium Khan Krupa Shingada Shreya Podder Harpreet Singh Bryan S. Benn Steven Verga Elizabeth Malsin Jonathan S. Kurman

Alveolar–pleural or broncho-pleural fistulas, leading to persistent air leaks (PALs), are associated with prolonged hospitalization and substantial morbidity. While guidelines advocate surgical repair as the primary treatment, its efficacy is limited. For patients recently subjected to thoracic surgery or those for whom surgery is contraindicated due to severe illness, viable treatment alternatives have been lacking. This article reviews the newer and less invasive treatment options for PALs. Further research is crucial, including randomized controlled trials comparing these options, and long-term monitoring of intervention outcomes is warranted.

Journal of Respiration doi: 10.3390/jor6020007

Authors: Lukas Neumann Christine Wagenlechner Peter Starzengruber Daniela Gompelmann Marco Idzko Ahmed El-Gazzar

Background: Proton pump inhibitors (PPIs) have been associated with lung dysbiosis and increased respiratory risk. Micro-aspiration is a proposed mechanism, but reliable biomarkers remain elusive. This study evaluates the potential of fluorescein as a biomarker of micro-aspiration and PPI-associated pulmonary risk. Methods: We conducted a retrospective analysis of 137 bronchial washing fluid samples from patients with pulmonary conditions to assess microbial colonization in relation to PPI use. Bacterial burden was determined by culture and PCR and categorized as 0, 1 or ≥2 pathogens. Micro-aspiration was evaluated by quantifying fluorescein-laden macrophages in bronchoalveolar lavage following oral fluorescein administration. Associations between PPI use, fluorescein levels and pathogen burden were analyzed using adjusted ordinal regression models. Results: PPI use was associated with higher odds of increased pathogen burden, though not statistically significant (OR = 1.40, 95% CI: 0.71–2.75, p = 0.33). Fluorescein-laden macrophages were higher in PPI users (41.5 versus 31.2 ng/mL), but showed no meaningful correlation with pathogen load (p = 0.09). Corticosteroid therapy was significantly associated with Gram stain results (OR = 2.37, 95% CI: 1.12–5.15, p = 0.03). Conclusions: These findings suggest a potential link between PPI use and airway colonization. Fluorescein shows promise as a biomarker for micro-aspiration, but its clinical utility requires further validation.

Journal of Respiration doi: 10.3390/jor6010006

Authors: Amr Seifelnasr Xiuhua Si Jinxiang Xi

Background: Accessory ostia (AOs) can notably alter maxillary sinus ventilation, yet configuration-specific effects remain unclear. This study quantified how AO location and orientation regulate sinus ventilation using in vitro measurements and numerical analyses. Methods: One patient-specific sinonasal geometry (control) was used to reconstruct five models with varying AO numbers, locations, and orientations (AO-F, AO-FC, AO-F30, AO-B, AO-FB). E-vapor was used as a visual tracer for sinus clearance under breath-hold and quiet breathing conditions. Complementary simulations characterized flow dynamics and sinus ventilation rates. Results: Both inhalation and AO presence accelerate e-vapor clearance for all conditions considered. The e-vapor clearance time in AO-FB decreases from 51 s under breath-hold to 29 s under quiet breathing (1 m/s). Configuration-wise, posterior AO ventilates the sinus faster than anterior AO, with dual anterior–posterior ostia (AO-FB) consistently performing the best. Among the three anterior AO, an uptilt AO ventilates the sinus faster than a parallel one, which is in turn faster than an AO located closer to the natural ostium (NO), i.e., AO-F30 > AO-F > AO-FC. CFD predictions provide a mechanistic understanding of the configuration-specific differences observed in vitro. Flow patterns in the ostium–sinus region, as well as the ventilation rate and driving pressure, show high sensitivities to AO location and orientation. At 1 m/s, the predicted AO-NO pressure drop ranges 2–18 mPa, with the lowest in AO-FC and highest in AO-B. Conclusions: The high sensitivity of sinus ventilation to AO configurations underscores the clinical importance of examining NO-adjacent openings in surgical planning and physiological interpretation.

Journal of Respiration doi: 10.3390/jor6010005

Authors: Stiliani Andreadou Georgia Tziouvara Georgios Mitsiou Aphrodite Evangelodimou Stavros Dimopoulos Irini Patsaki

Background/Objective: Post-COVID survivors present significant respiratory deficiency that has been associated with ongoing shortness of breath and impaired lung function. Inspiratory muscle training (IMT) is increasingly used in survivors of COVID-19 rehabilitational programs as a means to facilitate recovery of the respiratory system. Yet, its home-based effectiveness across clinically relevant outcomes remains unclear. This systematic review aimed to present current evidence on home- or tele-delivered IMT in the post-COVID-19 population. Methods: PubMed, Scopus, Cochrane library and Science Direct were systematically searched for studies evaluating home-based (or telerehabilitation) IMT, alone or as part of a respiratory muscle training program, in adults with post-COVID-19 symptoms. The primary outcome was inspiratory muscle strength. Secondary outcomes included dyspnea, pulmonary function, exercise capacity and health-related quality of life. The methodological quality of the included studies was assessed via the PEDro scale. Owing to clinical and methodological heterogeneity, we performed only a qualitative synthesis. Results: Eight studies met the inclusion criteria. Two included both inspiratory and expiratory muscles training and three included physical training as well. The methodological quality was found to be good. IMT consistently increased inspiratory muscle strength across trials. Respiratory muscle training (RMT) programs that combined inspiratory and expiratory training also improved maximal expiratory pressure. IMT reduced dyspnea versus control/sham or baseline and several studies reported improvements in exercise capacity and physical function. Spirometry/DLCO changes were small or null in most cohorts. HRQoL gains were domain-specific in anxiety and depression. Adherence was generally good. No serious adverse events attributable to IMT were reported. Conclusions: Home-based IMT for adults with post-COVID-19 conditions is safe and seems to improve inspiratory muscle strength and dyspnea, with signs of benefit for exercise capacity, physical function, and selected HRQoL domains. Effects on ventilatory efficiency and conventional lung function appear limited. Future multicenter, sham-controlled RCTs should further explore the characteristics of IMT, employ core outcome sets, include longer follow-up, and predefine phenotype-based subgroups.

Journal of Respiration doi: 10.3390/jor6010004

Authors: Alexandru Stoichita Beatrice Mahler Silviu Vlasceanu Oana Parliteanu Justina Antonela Dragomir Mara Balteanu Alexandru Daniel Radu Cristina Teleaga Dragos Baiceanu Traian Constantin Panciu Mosteanu Madalina Elmira Ibraim Madalina Mariuca Ciupan Adriana Iliesiu Mihaela

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause persistent, multisystem complications collectively termed long COVID. Cardiovascular sequelae are among the most clinically significant yet remain incompletely characterized. This review aimed to synthesize current evidence on objective cardiovascular outcomes in long COVID and explore underlying mechanisms. Methods: A systematic review was conducted using PubMed, Scopus, and Web of Science for studies published between January 2020 and March 2024. Search terms included “COVID-19,” “long COVID,” “post-acute sequelae,” “cardiovascular,” “echocardiography,” “biomarkers,” and “imaging.” Only studies reporting at least one cardiovascular outcome, defined as either objectively measured parameters (e.g., echocardiography, cardiac biomarkers, ECG findings, or vascular function indices) or clinically relevant cardiovascular symptoms during follow-up, were included. From 412 identified records, ten recent, high-quality studies with a primary cardiovascular focus were selected. This systematic review was conducted in accordance with the PRISMA 2020 guidelines. Results: Long COVID is associated with subclinical myocardial dysfunction, arrhythmias, endothelial injury, vascular stiffness, and a prothrombotic state. Reported findings included reduced left ventricular ejection fraction, impaired global longitudinal strain, increased arterial stiffness, elevated cardiac biomarkers, new-onset hypertension, and persistent ECG changes, even in non-hospitalized patients without prior cardiovascular disease. Proposed mechanisms include myocardial inflammation, endothelial dysfunction, renin–angiotensin–aldosterone system dysregulation, autonomic imbalance, and chronic inflammation. Secondary bacterial and fungal infections were noted in critically ill survivors but did not fully explain the breadth or persistence of symptoms. Conclusions: Long COVID is a heterogeneous entity with substantial cardiovascular implications across all levels of acute disease severity. Early detection through longitudinal monitoring, standardized definitions, and multidisciplinary care is essential to reduce long-term cardiovascular risk.

Journal of Respiration doi: 10.3390/jor6010003

Authors: Tarneem M. Alghamdi Mohammed M. Mergani Habib Abdulnabi Abdulaziz K. AlNaimi Mohammed D. Al Shubbar Hisham Y. Alouhali Mahmoud I. Mahmoud

Urinothorax, the presence of urine in the pleural space, is an exceptionally rare cause of pleural effusion, with fewer than 100 cases described in the literature. It most often follows trauma or urological procedures, though obstructive uropathy is also a recognized mechanism. We report an 83-year-old man with chronic kidney disease and benign prostatic hyperplasia who presented with acute dyspnea and a massive right-sided pleural effusion. Thoracentesis yielded clear yellow fluid with an ammonia-like odor, while imaging revealed chronic bladder outlet obstruction with bilateral hydroureteronephrosis. Despite inconclusive scintigraphy, the effusion resolved completely after urinary decompression with Foley catheterization, confirming the diagnosis. This case underscores the diagnostic challenges of urinothorax, which may be overlooked due to its rarity and variable biochemical profile, and highlights the importance of correlating clinical, radiologic, and pleural fluid findings. Early recognition is crucial, as timely relief of urinary obstruction provides both definitive diagnosis and curative treatment.

Journal of Respiration doi: 10.3390/jor6010002

Authors: Christopher N. Nemeh William F. Parker Douglas K. Hogarth Ajay A. Wagh

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity, mortality, and healthcare utilization. Lung volume reduction surgery improves outcomes in a select cohort but portends high morbidity. Bronchoscopic lung volume reduction (BLVR) is a less invasive, reversible manner of lung volume reduction, using one-way valves to improve lung function, quality of life, and exercise capacity. Nevertheless, knowledge gaps persist regarding factors that predict procedural success. Methods: We retrospectively reviewed 142 patients who underwent BLVR at the University of Chicago between December 2018 and July 2024 to assess the relationship between comorbidities and procedural outcomes. Using logistic and multinomial regression, we determined odds ratios (ORs) for a binary outcome of success and failure and relative risk ratios (RRRs) for failure sub-categories relative to procedural success. Results: We observed a procedural success rate of 48.1% and pneumothorax prevalence of 21.8%. After adjusting for age, sex, race, and body mass index (BMI), comorbidities associated with procedural failure included chronic kidney disease (CKD), congestive heart failure (CHF), anemia, and a BMI, Obstruction, Dyspnea and Exercise (BODE) Index of 5 or greater. Obstructive sleep apnea (OSA) was associated with procedural success. Conclusions: Comorbidities associated with dyspnea appear to have a significant effect on procedural success in BLVR.

Journal of Respiration doi: 10.3390/jor6010001

Authors: Thisarana Wijayaratne Akash Mavilakandy Faye Hinchcliffe Sarah Johnstone Rajini C. Sudhir Rakesh K. Panchal

(1) Background: Indwelling pleural catheters (IPCs) with vacuum-based drainage can cause pain, especially in patients with a non-expandable lung (NEL). This evaluation assessed whether the Passio™ digital drainage system offers a viable alternative for patients experiencing pain during IPC drainage. (2) Methods: All IPC patients between November 2023 and April 2024 completed questionnaires assessing pain severity on a 10-point visual analogue scale (VAS) at four points during drainage. Patients reporting drainage-related pain at the 2-week post-IPC appointment had their existing valve replaced with a Passio™ valve (n = 5). (3) Results: Twenty-seven patients (59% male) were included in this analysis. The mean VAS scores for pain with a standard vacuum bottle were not statistically different at mid-drainage and the end of drainage compared with pre-drainage. Patients who experienced pain with the vacuum bottle (n = 5) had higher mean VAS scores at mid-drainage (51.68 mm ± 16.29; p = 0.13), end of drainage (46.68 mm ± 19.45; p = 0.19), and 10 min post-drainage (61.38 mm ± 9.81; p = 0.06) compared with pre-drainage (9.16 mm ± 4.01). Post-Passio™ valve replacement (n = 5), patients had a lower VAS pain score mid-drainage (20.15 mm ± 9.34; p = 0.25), end of drainage (27.28 mm ± 12.69; p = 0.84), and 10 min post-drainage (14.81 mm ± 3.33; p = 0.0079) when compared with vacuum bottle drainage. There were no complications with the Passio™ drainage system. (4) Conclusions: Controlled pleural drainage using a digital drainage device such as Passio™ may have a role in IPC patients who experience pain with vacuum bottle drainage, especially in those with an NEL.

Journal of Respiration doi: 10.3390/jor5040020

Authors: Alberto García de la Fuente Ebymar Arismendi Mariona Pascal César Picado

The relationship between asthma, infections, and immunodeficiencies is complex and affects disease progression. Immune deficiencies can occur independently or because of the inflammatory processes associated with asthma. Early viral infections like respiratory sinticial virus and rhinovirus trigger asthma attacks, while bacteria such as Haemophilus influenzae, Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydia pneumoniae worsen airway inflammation. People with asthma often have defects in innate (mucociliary clearance, interferons, defensins, NK cell, and eosinophils) and adaptive immunity such as immunoglobulin (Ig) deficiencies, making them more vulnerable to lung infections. Combined and selective deficiencies of IgA, IgG, IgM, and IgE are linked to higher asthma rates and reduced effectiveness of treatments, but immunoglobulin therapy can help control symptoms. Biologic therapies also decrease asthma exacerbations during periods of high viral activity by boosting immune responses and airway defenses. However, the link between asthma and higher infection risk is not well studied or understood, so guidelines do not recommend routinely checking for immunodeficiencies in cases of poor treatment response. Further investigation is required to elucidate these relationships and enhance management approaches.

Journal of Respiration doi: 10.3390/jor5040019

Authors: Esther S. Kim Janice Wang

Allergic bronchopulmonary aspergillosis (ABPA) is mediated by hypersensitivity reactions to Aspergillus fumigatus, which is ubiquitous in the environment. People with Cystic Fibrosis (PwCF) are at an increased risk for developing ABPA, which can lead to frequent pulmonary exacerbations and progressive decline in lung function. In the age of highly effective modulator therapies (HEMT), PwCF have improved clinical outcomes and overall life expectancy, but they continue to suffer from comorbidities such as ABPA, which may be difficult to diagnose and treat. Establishing the diagnosis of ABPA in PwCF requires high clinical suspicion due to similarities in symptoms with the underlying disease. First-line treatment involves corticosteroids and anti-fungals, which have multiple side effects and drug interactions, especially with HEMT. Given this challenge, biologics have gained attention as potential agents directly targeting the Th-2 inflammatory pathway of ABPA with good tolerability and without significant drug interactions with HEMT. In this review, we discuss the diagnostic process and management of ABPA in PwCF, including a brief overview of the current literature on biologic agents.

Journal of Respiration doi: 10.3390/jor5040018

Authors: Ismael Matus Sameer Akhtar Vamsi Matta

Background: The incidence of iatrogenic pneumothorax (IPTX) following transbronchial lung cryobiopsy (TBLCB) ranges from 1.4% to 20.2%. While chest X-ray (CXR) is the standard imaging modality to exclude IPTX, thoracic ultrasound (TUS) has demonstrated superior accuracy in detecting pneumothorax across various contexts. This study evaluates TUS as a reliable alternative to routine CXR for ruling out IPTX after TBLCB. Methods: A retrospective observational study included 51 patients undergoing ambulatory TBLCB. Pre- and post-TBLCB TUS were performed. CXR was reserved for cases where TUS findings were inconclusive (absence of sliding lung [SL] and seashore sign [SS] in any lung zones) or if patients exhibited symptoms or signs of IPTX. Results: TUS findings were concordant in 44 (86.1%) patients, of whom 42 (95.5%) did not require CXR. Two patients (4.5%) with symptomatic IPTX were identified and managed. Among the seven patients (13.7%) requiring CXR due to inconclusive TUS or symptoms, five (71.4%) were negative for IPTX, and two (28.6%) had asymptomatic IPTX. Conclusion: Our TUS protocol effectively ruled out clinically significant IPTX, eliminating routine CXR in 95.5% of patients. TUS is a safe alternative to CXR post-TBLCB, with CXR reserved for inconclusive TUS findings or symptomatic cases.

Journal of Respiration doi: 10.3390/jor5040017

Authors: Michał Panek Robab Breyer-Kohansal Paschalis Steiropoulos Peter Kopač Maciej Wojakiewicz Tomasz Dębowski Christer Janson Maciej Kupczyk

Background: Triple therapy (long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs) and inhaled corticosteroids (ICSs)) is a recommended treatment for moderate-to-severe asthma at GINA Steps 4 and 5. However, little is known about the acceptance and use of triple therapy in everyday practice. The EU-LAMA Survey assessed specialists’ knowledge and views on triple therapy in daily practice. Methods: A 19-question survey was administered to 630 pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland (58%), Greece (27%), Sweden (6.3%), Slovenia (5.4%), and Austria (3.7%) using a dedicated online platform and computer-assisted web interviews. Results: The majority of the physicians were pulmonologists (59%), followed by allergologists (15.7%). For uncontrolled asthma at GINA Step 4, 81% of the respondents preferred increasing the ICS dose to the maximum level, whereas 76% opted to add LAMAs to medium-dose ICSs. At GINA Step 5, 79% of the respondents chose LAMAs first, followed by biological therapy (51%). Oral corticosteroids were favored over increasing the ICS dose and adding LAMAs. Triple therapy was mostly administered in one inhaler (70% and 82% at GINA Steps 4 and 5, respectively). Barriers to the use of LAMAs included a lack of reimbursement (31%), unclear guidelines (24%), lack of experience (18%), insufficient evidence (13%), fear of step-up regimens (10%), and the ease of increasing ICS doses (9%). Conclusion: Many physicians continue to rely on oral corticosteroids at GINA Steps 4 and 5 and infrequently refer patients to triple therapy or biological treatments at GINA Step 5.

Journal of Respiration doi: 10.3390/jor5040016

Authors: Luigi Cofone Marise Sabato Chiara Colombo Stefania Scalingi Antonio Montesi Lorenzo Paglione Federica Patania

Introduction: Radon is a radioactive noble gas formed from uranium decay in the Earth’s crust. The most significant isotope, 222Rn, emits alpha particles capable of damaging lung tissue and inducing cancer. Radon exposure is affected by geophysical and building characteristics and is recognized as a Group 1 carcinogen by the IARC. Despite regulatory thresholds (e.g., EURATOM standards), health risks remain. Various mitigation methods aim to reduce indoor radon exposure and its impact. Materials and Methods: This systematic review followed PRISMA guidelines. PubMed, Scopus, and Web of Science were searched up to 28 February 2025, using a defined string. Studies with original data on radon exposure and lung cancer risk or mitigation efficacy were included. Independent screening and quality assessment (Newcastle–Ottawa Scale) were conducted by multiple reviewers. Results: Of the 457 studies identified, 14 met the inclusion criteria. Eleven of these investigated the link between indoor radon and lung cancer risk, and three evaluated mitigation strategies. Radon levels were commonly measured using passive alpha track detectors. Levels varied depending on geographical location, season, building design and ventilation, these were higher in rural homes and during the colder months. Case–control studies consistently found an increased lung cancer risk with elevated radon exposure, especially among smokers. Effective mitigation methods included sub-slab depressurisation and balanced ventilation systems, which significantly reduced indoor radon concentrations. Adenocarcinoma was the most common lung cancer subtype in non-smokers, whereas squamous and small cell carcinomas were more prevalent in smokers exposed to radon. Discussion and Conclusions: This review confirms the robust association between indoor radon exposure and lung cancer. Risks persist even below regulatory limits and are amplified by smoking. While mitigation techniques are effective, their application remains uneven across regions. Stronger public education, building codes, and targeted interventions are needed, particularly in high-risk areas. To inform future prevention and policy, further research should seek to clarify radon’s molecular role in lung carcinogenesis, especially among non-smokers.

Journal of Respiration doi: 10.3390/jor5030015

Authors: Pranav Kumar Matthew Hiskens Yi Tat Lo Muhammad Jawwad Nazmi Sarah Wright Lauren McGrath

Background/Objectives: Asthma remains a prevalent cause of emergency department (ED) visits worldwide, necessitating prompt and effective intervention to prevent severe morbidity and mortality. This study evaluates the management of asthma patients presenting to the ED, focusing on clinical assessment, treatment strategies, diagnostic evaluations, and discharge practices. Methods: This retrospective audit was conducted in a regional hospital in Queensland, Australia. All ED patients between July 2023 and June 2024 with a diagnosis of asthma were included. Findings were benchmarked against international asthma guidelines to assess adherence to best practice. Results: A total of 199 patients were included. This study found that bronchodilator therapy was administered in 92.5% of cases and systemic steroids were given to 73.4% of patients, aligning with guidelines. However, significant deficiencies were noted in using objective lung function assessments, with only 1% of patients undergoing peak expiratory flow measurement and none undergoing spirometry, despite guideline recommendations advocating for their routine use. Additionally, inhaled corticosteroid prescriptions upon discharge were recorded in 19.6% of cases, compared to the recommended target of over 80%. There was a 6% relapse rate within a month of ED discharge. Conclusions: These gaps indicate potential areas for improvement, particularly in structured airflow assessment and post-discharge asthma management.

Journal of Respiration doi: 10.3390/jor5030014

Authors: María Belén Noboa-Sevilla Fernanda Hernández-González Sandra Cuerpo-Cardeñosa Xavier Alsina-Restoy Nancy Pérez-Rodas Alejandro Frino-García Miguel Alonso-Villares Elvis Matheus-Ramírez Jacobo Sellarés

Progressive pulmonary fibrosis (PPF) is a clinical syndrome associated with worsening quality of life and increased mortality among patients with various interstitial lung diseases. This review aims to update the concepts and criteria that adequately define PPF, aiming to facilitate earlier recognition and optimize clinical management. Fibrosing interstitial lung disease (ILD-f) can progress over time despite optimal management of the underlying conditions. Current criteria for defining PPF include worsening respiratory symptoms, decline in pulmonary function tests (particularly forced vital capacity and diffusing capacity), and radiographic progression over a 1-year follow-up period. However, implementation of these criteria in clinical practice poses challenges. This review discusses the limitations of current evaluation methods and proposes future directions, including the need for validated symptom assessment tools, standardization of pulmonary function testing, and improvements in quantitative radiological evaluation methods.

Journal of Respiration doi: 10.3390/jor5030013

Authors: Menkeoma Laura Okoli Ibuchim Chinemerem Okoli Abuoma Chisom Okoli Ikechukwu Umezurike Celestine Ishiekwene

Background: Community-acquired pneumonia in the United States accounts for over five million cases annually, with an estimated one million hospitalizations. About two million of these annual cases and over 100,000 annual hospitalizations are caused by mycoplasma pneumonia. Although mycoplasma can sometimes present as a benign disease, it can cause severe complications, which are referred to as pulmonary and extrapulmonary complications. This study aims to identify independent predictors of Mycoplasma pneumoniae infection among adult patients in our facility in East Texas. Methods: This retrospective cohort study used data from the electronic health record (EPIC Systems). Multivariate analyses were conducted to determine variables independently associated with mycoplasma pneumonia. The main outcome variable was the presence of mycoplasma pneumonia as indicated by serology testing. Results: Among 1714 adult patients in our study population who underwent antibody testing, 297 (17.3%) tested positive for mycoplasma pneumonia. Mycoplasma pneumonia was significantly associated with age, sex, race, season, and tobacco use after controlling for other variables. Adults who do not use tobacco had lower odds of having mycoplasma pneumonia compared to adults who are currently using tobacco (OR = 0.64, C.I. = 0.48–0.75). Also, these adults are more likely to have MP during non-respiratory season as compared to respiratory season (OR = 1.25, C.I. = 1.10–1.61). Conclusions: Tobacco use, season, age, race, and sex were all significant predictors of mycoplasma pneumonia. These findings highlight target areas for health care professionals and organizations to tackle to help improve patient health outcomes.

Journal of Respiration doi: 10.3390/jor5030012

Authors: Madiha Ajaz Indu Singh Lada Vugic Rati Jani Shashya Diyapaththugama Natalie Shilton

Asthma is a persistent ailment that impacts the respiratory system and stands as a formidable public health challenge globally. Inhaled corticosteroids and bronchodilators, while effective in asthma management, are accompanied by side effects and high costs. Recently, nutraceuticals have gained significant attention as adjuvant therapy due to their promising outcomes. Given the antioxidant properties, nutrient richness, and an array of health benefits, beetroot and its bioactive compounds have been tested as an adjuvant therapy for asthma management. Although its main bioactive compound, betalains (betanin), has demonstrated promising results in mouse studies, beetroot juice has been found to worsen asthma. This review investigated the full spectrum of active compounds associated with beetroots to understand the underlying factors contributing to the conflicting findings. The finding suggests that individual bioactive compounds, such as phenolic compounds, flavonoids, nitrates, betalains, saponins, vitamins, fiber, and carotenoids, possess asthma-managing properties. However, the consumption of juice may exacerbate the condition. This discrepancy may be attributed to the presence of sugars and oxalates in the juice, which could counteract the beneficial effects of the bioactive compounds.

Journal of Respiration doi: 10.3390/jor5030011

Authors: Anass Benfares Abdelali yahya Mourabiti Badreddine Alami Sara Boukansa Ikram Benomar Nizar El Bouardi Moulay Youssef Alaoui Lamrani Hind El Fatimi Bouchra Amara Mounia Serraj Mohammed Smahi Abdeljabbar Cherkaoui Mamoun Qjidaa Ahmed Lakhssassi Mohammed Ouazzani Jamil Mustapha Maaroufi Hassan Qjidaa

Background: This study aimed to develop a nomogram based on the most relevant clinical, CT, and radiomic features comprising 11 key signatures (2 clinical, 2 CT-based, and 7 radiomic) for the non-invasive prediction of the EGFR mutation status and to support the timely initiation of tyrosine kinase inhibitor (TKI) therapy in patients with non-small cell lung cancer (NSCLC) adenocarcinoma. Methods: Retrospective real-world data were collected from 521 patients with histologically confirmed NSCLC adenocarcinoma who underwent CT imaging and either surgical resection or pathological biopsy for EGFR mutation testing. Five Random Forest classification models were developed and trained on various datasets constructed by combining clinical, CT, and radiomic features extracted from CT image regions of interest (ROIs), with and without feature preselection. Results: The model trained exclusively on the most relevant clinical, CT, and radiomic features demonstrated superior predictive performance compared to the other models, with strong discrimination between EGFR-mutant and wild-type cases (AUC = 0.88; macro-average = 0.90; micro-average = 0.89; precision = 0.90; recall = 0.94; F1-score = 0.91; and accuracy = 0.87). Conclusions: A nomogram constructed using a Random Forest model trained solely on the most informative clinical, CT, and radiomic features outperformed alternative approaches in the non-invasive prediction of the EGFR mutation status, offering a promising decision-support tool for precision treatment planning in NSCLC.

Journal of Respiration doi: 10.3390/jor5030010

Authors: Satoshi Kawakami Taro Shirakawa Shoichi Wajima Yusuke Segawa Yoshitaka Fukuzawa Kou Sakabe

Interstitial pneumonia is a general term for diseases in which inflammation occurs mainly in the interstitium of the lung. It is also pointed out that interstitial pneumonia reduces alveolar function and makes it difficult to take in oxygen through inspiration, causing symptoms such as dyspnea and coughing, which may eventually lead to respiratory failure. At present, there is no effective treatment, and only conservative treatment exists. This time, we report that the therapeutic effect was confirmed in patients with interstitial pneumonia who took platinum palladium. In this case, improvement tendencies were observed in patients with Idiopathic pulmonary fibrosis (IPF), but improvement tendencies were also observed in many other lung diseases. In order to explore the mechanism, AMPK was measured at the in vitro level, and blood KL-6 and hydrogen peroxide levels in the patient were measured at the in vivo level. AMPK values were significantly elevated by more than 800%, and KL-6 and hydrogen peroxide levels were also significantly decreased by drinking platinum palladium. Platinum palladium exhibits a strong antioxidant effect and is the only substance in the world that can approach all four types of active oxygen. In addition, when it was actually administered to patients, there were cases of dramatic improvement, and it was confirmed that KL-6, a parameter of lung function, decreased in 16 out of 32 patients, and furthermore, oxygen inhalation was completed. Patients were also seen. It was suggested that increasing the number of cases in the future may help improve interstitial pneumonia.

Journal of Respiration doi: 10.3390/jor5030009

Authors: Jebelle Sutanto Grace Mussell Daniel Mitchell Wei Hann Ong Avinash Aujayeb

Introduction: Computed tomography-guided biopsies (CTGB) are essential in diagnosing various conditions, particularly in respiratory medicine, with lung cancer being a primary focus. A significant complication associated with CTGB is pneumothorax, which can occur in up to 26% of cases. At Northumbria Healthcare NHS Foundation Trust, a large interventional service collaborates closely with radiologists and respiratory physicians. This study aims to evaluate the incidence of pneumothorax following CTGB. Methods: A retrospective service review was conducted on all lung parenchymal CTGBs performed between April 2011 and July 2023, with approval from the local information governance. Demographic data and clinical outcomes were analyzed using descriptive statistics. Continuous variables are presented as medians with interquartile ranges (IQR), while categorical variables are reported as frequencies and percentages. Results: A total of 1492 CT-guided lung biopsies were analyzed. The median age of patients was 72 years (IQR 10.5), and 50.9% were male. Pneumothorax occurred in 23.8% (n = 355) of cases. Of these, 159 (44.8%) were detected on post-biopsy CT scans. The average number of pleural passes was 1.8 (range 1–4). Among those with pneumothorax, 53.6% had radiologically evident emphysema. The median forced expiratory volume in 1 s (FEV1) was 1.97 L (IQR 1.04). Sixty-seven percent (n = 234) of patients had no pleural contact, and the median lesion size was 26 mm (IQR 24). Seventy-two percent (n = 255) of lesions with pneumothoraces were less than 3 cm deep. Forty-four percent of biopsies were performed using 18 French gauge tru-cut needles. Of the 355 pneumothoraces, 89% (n = 315) were managed conservatively, with 42 requiring pleural intervention (41 small-bore 12 Fr intercostal chest drains and one pleural vent). Symptoms were initially present in 40 cases, and two cases developed symptoms up to 7 days post-procedure. Conclusions: The incidence of pneumothorax is consistent with expected rates, with more occurrences observed in biopsies of smaller lesions lacking pleural contact, lesions with surrounding emphysema, and cases requiring multiple pleural passes. FEV1 does not appear to influence the risk of pneumothorax. Conservative management is generally effective, without significant complications.

Journal of Respiration doi: 10.3390/jor5030008

Authors: Ahmad Raza Nayab Nadeem Christian Cardillo Lijo Illipparambil Aamir Ajmeri

Background: DLco remains one of the most commonly performed tests in the pulmonary lab. An isolated reduction in DLco is a unique abnormality with specific differentials when evaluating a patient with dyspnea. There remains a significant misunderstanding amongst young pulmonologists and pulmonary trainees regarding DLco and its relationship with alveolar volume and kco. Objective: This review aims to provide a physiological basis for the DLco test and bust the myth of “DLco corrected for lung volume.” Method: A systematic review of the available literature regarding alveolar gas-exchange physiology, measurement methods of DLco, the interplay of different variables associated with it, and the causes of its reduction was performed. Focused physiological data were used to put together a comprehensive review of isolated reductions in DLco. The second part of this review addresses the critical and interdependent relationship between DLco and alveolar volume (VA). Results: DLco has a unique relationship with lung volume that needs to be considered while interpreting its value. Diffusion capacity per unit volume (kco) is an independent factor that, when combined with DLco and VA, helps accurately interpret the test and narrow down differentials. Conclusion: DLco is an extremely valuable test and an important prognostic tool in many patients with dyspnea. An isolated reduction in DLco is increasingly recognized these days as an early marker of detection for various pulmonary parenchymal and vascular diseases. A detailed physiopathological explanation, followed by the proposed algorithm, should help pulmonary physicians and trainees understand and implement DLco’s relationships in their daily patient care.

Journal of Respiration doi: 10.3390/jor5020007

Authors: Carl Lawrence Arenos Franessa Ysabel Dianne Chan Huan-Jacinto Josephine Anne Lucero Frederic Ivan Ting Marvin Jonne Mendoza Madelaine Amante Danielle Benedict Sacdalan John Paulo Vergara

Current treatments for metastatic non-small cell lung cancer (NSCLC) have improved survival but remain non-curative, primarily aiming to control disease and to extend life. Structured exercise has demonstrated clinical and quality-of-life benefits in early-stage NSCLC. This systematic review assesses the impact of adjunctive exercise programs on health-related quality of life (HRQoL) in advanced NSCLC patients, with safety as a secondary outcome. Of 1168 studies screened, 13 met the inclusion criteria. All eligible studies were included in the systematic review, and three underwent meta-analysis. Using Synthesis Without Meta-analysis (SWiM), the findings were heterogeneous: four studies showed positive outcomes, two had mixed results, and seven showed negative outcomes. Meta-analysis of studies utilizing the EORTC-C30 tool demonstrated a positive mean difference of 1.57 (95% CI: 0 to 3.14), indicating a trend toward HRQoL improvement. Safety analyses largely revealed no major adverse events related to exercise interventions. Future studies must therefore be designed to account for confounders intrinsic to the underlying disease of study participants to better determine both the efficacy and the safety of structured, adjunctive exercise programs in this patient population.

Journal of Respiration doi: 10.3390/jor5020006

Authors: Maria E. Ramos-Nino Abraham Agaya Obadiah Ifesinachi Ogochukwu Ozugha Prakash V. A. K. Ramdass

Observational studies suggest a comorbid link between asthma and endometriosis, but the evidence remains limited and inconsistent. This study presents a meta-analysis examining this association. A comprehensive search of literature databases was conducted through August 2024. Prevalence rates and odds ratios (ORs) were calculated to assess the relationship between asthma and endometriosis. For the prevalence analysis, sixteen studies, including 54,856 endometriosis cases and 300,613 controls, were included. The analysis yielded a prevalence of asthma in endometriosis patients of 14.9% (95% CI [10.3, 19.6], p < 0.001), with high heterogeneity (I2 = 99.9%). In the control group, asthma prevalence was 9.1% (95% CI [6.5, 11.6], p < 0.001, I2 = 99.9%). For the odds ratio (OR) analysis, twelve studies, including 295,845 endometriosis cases and 28,030,081 controls, were included. The meta-analysis demonstrated a significant association between asthma and endometriosis with an OR of 1.59 (95% CI [1.22, 2.07], p = 0.0007, I2 = 100%). Subgroup analyses stratified by study region and study type were also conducted. This meta-analysis suggests a significant association between asthma and endometriosis, indicating that common factors underlying these chronic inflammatory diseases may contribute to this comorbidity. The findings support the biological plausibility of this association.

Journal of Respiration doi: 10.3390/jor5020005

Authors: Kian Barari Xiuhua Si Rozhin Hajian Jinxiang Xi

Background/Objectives: Mask-wearing-induced discomfort often leads to unconscious loosening of the mask to relieve the discomfort, thereby compromising protective efficacy. This study investigated how leakage flows affect mask-associated thermoregulation and vapor trapping to inform better mask designs. An integrated ambience–mask–face–airway model with various mask-wearing misfits was developed. Methods: The transient warming/cooling effects, thermal buoyancy force, tissue heat generation, vapor phase change, and fluid/heat/mass transfer through a porous medium were considered in this model, which was validated using Schlieren imaging, a thermal camera, and velocity/temperature measurements. Leakages from the top and side of the mask were analyzed in comparison to a no-leak scenario under cyclic respiration conditions. Results: A significant inverse relationship was observed between mask leakage and facial temperature/humidity. An equivalent impact from buoyancy forces and exhalation flow inertia was observed both experimentally and numerically, indicating a delicate balance between natural convection and forced convection, which is sensitive to leakage flows and critical in thermo-humidity regulation. For a given gap, the leakage fraction was not constant within one breathing cycle but constantly increased during exhalation. Persistently higher temperatures were found in the nose region throughout the breathing cycle in a sealed mask and were mitigated during inhalation when gaps were present. Vapor condensation occurred within the mask medium during exhalation in all mask-wearing cases. Conclusions: The thermal and vapor temporal variation profiles were sensitive to the location of the gap, highlighting the feasibility of leveraging temperature and relative humidity to test mask fit and quantify leakage fraction.

Journal of Respiration doi: 10.3390/jor5010004

Authors: Radha Gopalaswamy Selvakumar Subbian

Tuberculosis (TB) is a leading cause of death from a single infectious agent in humans. The morbidity and mortality due to TB are further worsened by co-existing health conditions and the emergence of drug-resistant (DR-TB) cases. The WHO has declared TB as a global emergency and endorsed global efforts to improve diagnosis, and treatment while reducing the catastrophic cost in an EndTB strategy in 2013, with a vision to create a TB-free world. In the past decade, molecular diagnostic tools, such as nucleic acid amplification technologies (NAATs), have replaced the conventional smear microscopy of TB, thus offering better bacteriological confirmation and case detection along with drug resistance in pulmonary and extrapulmonary samples. Follow-on testing using a more advanced targeted next-generation sequencing (tNGS) system has improved the diagnosis of cases resistant to first- and second-line anti-TB drugs, including newer ones. TB treatment has been improved with the introduction of newer drugs including an all-oral regimen for DR-TB, thereby improving patient compliance. Improved TB prevention is achieved through the broadening of BCG vaccination as well as preventive therapy for asymptomatic, latent TB (LTBI) cases, which, otherwise, can reactivate to symptomatic disease. However, the recent goal of the WHO’s EndTB-2035 strategy has been met with significant challenges in the areas of implementing improved diagnosis and treatment modalities in resource-limited TB endemic countries. The complexity of global TB management is confounded by malnutrition, comorbidities with other infectious and non-infectious diseases, and the socio-economic landscape of vulnerable populations. Political commitment to universal health coverage (UHC), including service coverage and reduction in catastrophic cost, are some of the essential components that need to be addressed to achieve the EndTB strategy. In this perspective, we have highlighted the intricacies of global TB management and summarized some of the key challenges that may keep the WHO’s EndTB-2035 strategy on the fence.

Journal of Respiration doi: 10.3390/jor5010003

Authors: Cristina López-Riolobos Juan Riestra-Ayora Beatriz Raboso Moreno Nora Lebrato Rubio José María Diaz García Cristina Vaduva Indira Astudillo Rodríguez Leonardo Saldaña Pérez Fernando García Prieto Sara Calero Pardo Araceli Abad Fernández

ChatGPT (Chat-Generative Pre-trained Transformer) is an accessible and innovative tool for obtaining healthcare information. This study evaluates the quality and reliability of information provided by ChatGPT 4.0® regarding Obstructive Sleep Apnea (OSA), comparing it with responses from sleep medicine specialists. Thirty frequently asked questions about OSA were posed to ChatGPT 4.0® and two expert physicians. Responses from both sources (V1: AI and V2: Medical Experts) were blindly evaluated by a panel of six specialists using a five-point Likert scale across precision, relevance, and depth dimensions. The AI-generated responses (V1) achieved a slightly higher overall score compared to those from medical experts (V2), although the difference was not statistically significant (p > 0.08). These results suggest that both sources offer comparable quality and content. Additionally, ChatGPT’s responses were clear and easily understandable, providing an accessible explanation of OSA pathology.

Journal of Respiration doi: 10.3390/jor5010002

Authors: Jair Gutierrez-Herrera M. Angeles Montero-Fernandez Georgia Kokaraki Luigi De Petris Raul Maia Falcão Manuel Molina-Centelles Ricardo Guijarro Simon Ekman Cristian Ortiz-Villalón

Background/Objectives: Since the discovery of oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusions in colorectal cancer in 1986, their understanding has evolved, particularly in non-small-cell lung cancer (NSCLC) over the past five years. NTRK rearrangements, involving NTRK1, NTRK2, and NTRK3, drive tumorigenesis and have been identified in various adult and pediatric cancers, with over 80 different fusion variants in several type of cancers. Detecting these rearrangements is crucial for targeted therapy strategies. The aim of this study is detect, compare and analyse these mutations in NSCLC patients of a cohort of 482 cases from Karolinska University Hospital. Methods: We conducted an initial screening using pan-TRK immunohistochemistry (IHC) to analyze the material. Positive cases were further examined through whole-exome sequencing (WES) with next-generation sequencing (NGS) to confirm the presence of fusions. Additionally, to deepen our understanding, we utilized Ingenuity Pathway Analysis (IPA) software, an artificial intelligence-driven technology, to explore the molecular pathways involved in lung cancer. Results: TRK overexpression was detected in 4.56% of cases via IHC. Among 15 pan-TRK-positive cases, WES confirmed fusions in 3, revealing a higher prevalence of NTRK1 (6.6%) and NTRK2 (13.3%) fusions, while no NTRK3 fusions were observed. Conclusions: Our findings confirm the low prevalence of these neoplasms as well as the need for a molecular test to confirm rearrangements or other potentially treatable mutations and raise other questions regarding their clinical use. However, there is an acceptable correlation between pan-TRK IHC and NTRK mutations, but not enough to determine NTRK fusions.

Journal of Respiration doi: 10.3390/jor5010001

Authors: Austin Baird Rachel A. Umoren Steven A. White Megan Gray Taylor L. Sawyer

Background: There is a limitation in understanding complete cardiopulmonary function during moments of exhaustive exercise due to invasive measurement techniques. We asked how cardiopulmonary function is perturbed during times of exercise in different age cohorts: 6–11 and 11–18. We sought to broadly analyze how age and oxidative stress during exercise differ across age cohorts. Methods: We present a whole-body physiology model that connects the nervous, cardiovascular, respiratory, and oxygen transport and binding systems. We connect these models using a lumped parameter representation of the cardiovascular and respiratory systems. Results: we observe distinct age-related difference in physiological response to exercise. These responses consist of respiratory, cardiovascular, and nervous system perturbations that are distinct across these age groups.

Journal of Respiration doi: 10.3390/jor4040020

Authors: Daniel Jacob Smith Russell Vo Parker Lachowsky Ann Davis Isha Puri Sai Karan Vamsi Guda

Self-Expanding Metallic (SEM) Y stents are a newer form of stent that is gaining popularity outside the USA, but still has limited data, especially in a community medicine setting. This study analyzed efficacy and complication rates in 14 patients who had a SEM Y stent placed between August 2022 and June 2024 at Harris Methodist Hospital in Fort Worth, Texas for either central airway obstruction (CAO) or fistulae. Of the 14 patients, 11 were requiring supplemental oxygen or mechanical ventilation prior to stent placement. Post-stenting 42.9% had decreased oxygen requirements, 21.4% unchanged, 14.3% increased, and 21.4% remained on room air. Complications included mucus plugging (42.9%), infection (35.7%), and granulation tissue (14.3%). There was no statistically significant correlation between gender/age and complications (p = 0.879/0.490, respectively). Complication rates were similar when compared to silicone Y stents based on literature review. In conclusion, SEM Y stents are a safe and effective alternative stent intended for palliative treatment with similar success and complications that can be easily and effectively implemented in a community hospital, with the added benefit of being able to be placed with flexible bronchoscopy.

Journal of Respiration doi: 10.3390/jor4040019

Authors: Kavita Sivabalah Haval Balata Chris Craig Alaa Alsaaty Kevin Conroy Wei Hann Ong Avinash Aujayeb

The management of malignant pleural effusions (MPEs) has developed hugely since the publication of the management of an MPE: British Thoracic Society (BTS) Pleural Disease Guideline 2010. The presence of an MPE reflects advanced or metastatic disease (excluding malignant pleural mesothelioma) and thus the management of MPE often focuses on symptomatic relief of symptoms and improving quality of life. We provide a review of the 2023 BTS guidance in relation to malignant pleural effusions and specific points on imaging and systemic anti-cancer treatment by concentrating on a hypothetical patient vignette.

Journal of Respiration doi: 10.3390/jor4040018

Authors: Maria E. Ramos-Nino Prakash V. A. K. Ramdass

Background: Asthma is a respiratory disorder influenced by genetic and environmental factors. The rs7216389 polymorphism in the gasdermin B (GSDMB) gene on chromosome 17q21 has been implicated in asthma susceptibility with conflicting results. This meta-analysis aims to bring forward new findings on the association between this polymorphism and asthma across diverse populations and its potential as a genetic marker for asthma risk. Methods: A systematic review and meta-analysis were conducted through March 2024, and odd ratios were calculated. Results: The meta-analysis included 22 studies with a total of 9012 asthma patients and 11,657 controls. The results show an OR = 1.24, 95% CI [1.13, 1.37], p < 0.00001. Subgroup analyses stratified by age and ethnicity between asthma patients with T alleles vs. C alleles demonstrated an association between having the T allele and asthma susceptibility across Asian, Caucasian, and American minorities, but not among Arabs. Young asthma patients with the dominant allele (T) showed higher asthma risk than those with C allele or heterozygote TC, and to a higher extent than for adults. Conclusions: This meta-analysis indicates the importance of genetic factors in asthma in certain ethnicities and underscores the potential utility of the rs7216389 polymorphism as a genetic marker for asthma risk assessment.

Journal of Respiration doi: 10.3390/jor4040017

Authors: Lorelle Dismore Leah Taylor Christopher Hurst Avinash Aujayeb Hannah Poulter Katherine Swainston

Patients with a mesothelioma diagnosis often have relatively sedentary lifestyles and low physical activity. Reducing sedentary behaviour and being more active could be beneficial. A greater understanding of the factors associated with physical activity is needed to inform the development of interventions. Semi-structured interviews with patients with mesothelioma and informal carers were performed and analysed thematically. Three themes were generated: (1) the impact of disease burden and physical and psychological symptoms, (2) the psychosocial consequences and benefits of physical activity and (3) unpredictability and maintaining control. Participants had become increasingly sedentary during diagnosis and while undergoing treatment. Symptoms were key factors contributing to these reductions. Being less active reduced social connectedness and impacted psychological well-being. Some participants had lost confidence in being active and were worried about the potential negative consequences of doing more. Being able to walk was a priority, and they felt hopeful about increasing this in the future, but this depended on optimisation of symptoms. Clear guidance from healthcare professionals was needed to support engagement in physical activity. Declines in physical activity can have meaningful consequences for patients. Optimisation of symptoms is important to devise strategies to support patients with physical activity. Along with encouragement from healthcare professionals.

Journal of Respiration doi: 10.3390/jor4030016

Authors: Sagar Kumar Anita Mazloom Marialaina Carter FNU Manisha Jacek Polski Omar Alkharabsheh

Extramedullary myeloma with pulmonary and pleural involvement is rare and can present in different ways. Here we present two cases of extramedullary pulmonary disease in relapsed/refractory multiple myeloma. Background: Multiple myeloma remains an incurable disease with unmet need for new treatments for high-risk disease such as extramedullary plasmacytoma. Relapses can occur at different stages due to the heterogeneity of the disease. While relapsed/refractory disease can be challenging to treat, progression can also lead to extramedullary disease which indicates an aggressive form with poor outcomes. Pulmonary extramedullary disease can present in various ways, such as a lung mass, parenchymal infiltrates, pleural mass, or pleural effusion. Objective: Our case series highlights two different presentations of pulmonary extramedullary disease and a review of the treatment of relapsed/refractory myeloma. Our patients highlight the progression of their multiple myeloma due to the aggressive nature of their extramedullary disease. Their cases emphasize the importance of new targeted treatments to treat extramedullary disease and penta-refractory disease as there is no currently accepted standard regimen for this difficult to treat condition.

Journal of Respiration doi: 10.3390/jor4030015

Authors: Patrick Dakum Aderonke Agbaje Olugbenga Daniel Chukwuma Anyaike Obioma Chijoke-Akaniro Evaezi Okpokoro Samuel Akingbesote Christian Anyomi Adekola Adekunle Abiola Alege Moroof Gbadamosi Olutunde Babalola Charles Mensah Rupert Eneogu Austin Ihesie Debby Nongo Ademola Adelekan

This paper presents a formative assessment for the implementation of mobile portable chest X-ray (PDX) machines for tuberculosis (TB) contact tracing in the Oyo and Osun states, Nigeria. This descriptive qualitative study was carried out in eight local government areas, and 24 focus group discussions and 30 key informant interviews were conducted using a four-stage sampling technique to select participants. Validated transcribed notes were entered and analyzed using Nvivo. The respondents’ ages ranged from 17 to 85 years, with a mean age of 42.08 ± 14.9 years, and 4.0% had a postgraduate degree. The majority of government officials stated that deploying the PDX machine for screening at the community level is the best means for implementation because it will offer a level of proximity convenience to the TB contacts and assuage concerns about the cost of transportation to the health facility. In addition, it was suggested that TB community screening should be carried out with screening for other health conditions such as high blood pressure and diabetes. This portable X-ray machine intervention, therefore, should be implemented at the community level for contact tracing to allow more TB contacts living with the index patient to be screened without proximity and transportation constraints.

Journal of Respiration doi: 10.3390/jor4030014

Authors: Alex I. Halpern Mohadese Behtaj Elham Arbzadeh Keith D. Mortman

Primary pulmonary myxoid sarcoma (PPMS) is a rarely reported, low-grade malignant endobronchial tumor. We describe a case of PPMS in an asymptomatic 47-year-old female. We highlight the clinical and pathologic aspects of PPMS and its relationship with angiomatoid fibrous histiocytoma.

Journal of Respiration doi: 10.3390/jor4030013

Authors: Sapna Dixit Jyoti Bajpai Surya Kant Ajay Kumar Verma Puneet Prakash

Patients with metastatic breast cancer often have respiratory symptoms due to various causes. Trastuzumab is a drug used in the treatment of HER2/neu over-expressing breast cancer patients. Organising pneumonia is a type of idiopathic interstitial pneumonia that mimics infection or progressive disease and can be difficult to diagnose in the setting of malignancy. Making a correct diagnosis is of extreme importance since any delay in the treatment can result in significant adverse patient outcome. Here, we have described a case of organising pneumonia associated with the use of trastuzumab in metastatic breast cancer patients. On the basis of clinical data, including findings such as a decreased PaO2 level and findings on chest CT scan, these patients were diagnosed with drug-induced organising pneumonia. Although it is a rare adverse event associated with trastuzumab, it may cause rapid deterioration without preceding symptoms; hence, even though it is very rare, with an incidence of less than 2%, it is still crucial to intervene so as to prevent the occurrence of such an unfavourable outcome by means of close observation and early diagnosis along with an early withdrawal of the drug and an immediate commencement of corticosteroid therapy.

Journal of Respiration doi: 10.3390/jor4020012

Authors: Derek M. Clarke Katrina L. Curtis Kaden Harward Jared Scott Brendan M. Stapley Madison N. Kirkham Evan T. Clark Peter Robertson Elliot Chambers Cali E. Warren Benjamin T. Bikman Juan A. Arroyo Paul R. Reynolds

RAGE (receptor for advanced glycation end-products) represents a class of multi-ligand pattern recognition receptors highly expressed in the vertebrate lung. Our previous work demonstrated unique patterns of RAGE expression in the developing murine lung and regulation by key transcription factors including NKX2.1 and FoxA2. The current investigation employed conditional lung-specific upregulation via a TetOn transgenic mouse model (RAGE TG) and nontransgenic controls. RAGE expression was induced in RAGE TG mice throughout gestation (embryonic day, E0-E18.5) or from E15.5-E18.5 and compared to age-matched controls. High-resolution respirometry was used to assess mitochondrial respiration and context was provided by quantifying ATP and reactive oxygen species (ROS) generation. Lung lysates were also screened by immunoblotting for MAPK/PI3K signaling intermediates. RAGE upregulation increased mitochondrial oxygen consumption in the E0-E18.5 and E15.5-E18.5 groups compared to controls. RAGE TG mice also had increased ATP concentrations, which persisted even after controlling for oxygen consumption. In contrast, ROS generation was diminished in RAGE TG animals compared to controls. Lastly, in both RAGE TG groups, pERK and pp38 were significantly decreased, whereas pAKT was significantly elevated, suggesting that RAGE signaling is likely perpetuated via pAKT pathways. Together, these data demonstrate that despite lung hypoplasia in RAGE TG mice, the remaining tissue experiences a favorable shift in mitochondrial bioenergetics without excessive redox assault and a preference for AKT signaling over ERK or p38.

Journal of Respiration doi: 10.3390/jor4020011

Authors: Bharat Singh Bhandari Akshita Jain Soumit Sharma Gunjan Rana Bruce Fernando Sabath

Lung cancer, a major global cause of cancer-related deaths, demands continual advancements in diagnostic methodologies. This review delves into the transformative role of Robotic-Assisted Bronchoscopy (RAB) in redefining lung cancer diagnostics. As lung cancer screenings intensify, leading to a surge in pulmonary nodule diagnoses, navigational bronchoscopy, notably electromagnetic navigational bronchoscopy (ENB), faces persistent limitations. Examining key RAB platforms—Monarch™, Ion™ and the Galaxy System™—reveals their distinctive features, with RAB demonstrating superior diagnostic yields over traditional biopsy methods. However, challenges include CT-to-body divergence (CBCT) and divergent findings in diagnostic yield studies and a lack of head-to-head comparisons with non-RAB modalities. Future directions should explore RAB’s potential therapeutic applications, shaping the landscape of both diagnostics and therapeutics in lung cancer management.

Journal of Respiration doi: 10.3390/jor4020010

Authors: Thomas Presti Aleezay Asghar Nakul Ravikumar

Pleural infection, including empyema, continues to have a high morbidity. A deep understanding of the pathobiology and appropriate medical management is crucial to avoid complications and progression to the need for surgery. Over the last several decades, we have learned much about the pathophysiology, microbiology, and epidemiology of pleural infections. Management has changed considerably over the years with more recent clinical practices favoring minimally invasive interventions over surgery. Here we discuss in detail the pathophysiology of parapneumonic effusions as they progress from uncomplicated parapneumonic effusions to empyema and how this relates to their diagnosis and management. We review the microbiology and how it relates to recommended empiric antibiotic regimens. As intrapleural fibrinolytic therapy has become the cornerstone of management, we outline the literature on this topic dating back decades up to the most recent clinical trials and give our recommendations for management based on the literature.

Journal of Respiration doi: 10.3390/jor4020009

Authors: Sebastian Mactaggart Raheel Ahmed

Introduction: Those with cardiac sarcoidosis (CS) are at risk of sudden cardiac death (SCD), which may be prevented using an implantable cardioverter–defibrillator (ICD). There are limited data available that follow the post-procedural outcomes of patients with cardiac sarcoidosis (CS) who have had an ICD implanted. Areas Covered: This review highlights studies that focused on both appropriate and inappropriate therapies in those with an ICD, as well as device complications in this group. There were several variables, including age, sex, ventricular characteristics, and findings on cardiac imaging that were investigated and discussed as influencing factors in predicting appropriate and inappropriate therapies. Conclusions: Adverse events in those with an ICD and CS have been minimally reported in the literature. Individuals diagnosed with CS are at high risk of ventricular arrhythmia, with comparable rates of appropriate therapy but with a higher incidence of side effects and inappropriate therapy. The younger average age of CS patients in comparison to other ICD cohorts warrants the need for further, large-scale, prospective trials with periodic interim follow-ups focused on those with this condition.

Journal of Respiration doi: 10.3390/jor4020008

Authors: Christopher D. Williams Kirsten M. Holbrook Aryan Shiari Ali A. Zaied Hussam Z. Al-Sharif Abdul R. Rishi Ryan D. Frank Adel S. Zurob Muhammad A. Rishi

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted, comprising an initial 10-min OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 h after extubation. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs. 62%; p = 0.19) and were older (median, 70 vs. 67 years; p = 0.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs. 7.4 days; p = 0.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs. 1.1 days with usual care; p = 0.06) and shorter LOS in the intensive care unit (mean, 2.7 vs. 3.4 days; p = 0.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, −0.85 days; 95% CI, −1.65 to −0.06; p = 0.04). The OPE group had a lower percentage of postoperative complications (10% vs. 20%). Conclusions: OPE therapy after cardiac surgery is associated with decreased intensive care unit (ICU) and hospital LOS.

Journal of Respiration doi: 10.3390/jor4010007

Authors: Dylan Harrell David M. Chambers

Interventional pulmonology is a rapidly growing field with increasing demand. To meet this demand, training in interventional pulmonology is expanding. What started as a single training program without a standardized curriculum has grown to 40 accredited training programs with a well-defined curriculum that is now overseen by the Accreditation Council for Graduate Medical Education. As the field develops, research is being actively performed to develop validated competency assessment tools and describe the learning curves for pulmonary procedures. As research evolves, this information can be used to better standardize training in interventional pulmonology and move the field towards a competency-based training model.

Journal of Respiration doi: 10.3390/jor4010006

Authors: Sami I. Bashour Donald R. Lazarus

Airway stents, first developed in the 1980s, have become fundamental in managing a multitude of airway pathologies and complications within the field of interventional pulmonology. The primary function of an airway stent is to re-establish airway patency and integrity when obstruction, stenosis, anastomotic dehiscence, or fistulae develop as a result of various malignant or benign conditions. Nevertheless, airway stents are foreign bodies that can result in complications. In this review article, we will discuss airway stents and their ongoing role in the management of several malignant and benign diseases. We will describe indications for airway stenting and review the elements that must be taken into consideration for optimal patient and stent selection. Given the prevalence of data regarding therapeutic bronchoscopy and airway stenting in malignant airway obstruction, much of the discussion in this review will focus on stent placement for that indication. We will also review the data as it pertains to safety, efficacy, and complications after stent placement, and conclude with a discussion of the future applications and research avenues related to airway stents.

Journal of Respiration doi: 10.3390/jor4010005

Authors: Ali B. Rueschhoff Andrew W. Moore Maykol R. Postigo Jasahui

Lung cancer is the leading cause of cancer-associated death globally. Staging provides classification of the anatomic extent of cancer that is used consistently worldwide. Lung cancer staging is necessary for prognostication, to inform treatment options, and to allow accurate representation in clinical trials. Staging also separates operable from inoperable disease. Since its introduction in the 1970s, the Tumor, Node and Metastasis (TNM) Staging System has undergone significant revisions, with the latest version, the eighth edition, being effective internationally since 2017. Advances in bronchoscopic and thoracoscopic technologies have expanded procedures to diagnose lung cancer and accurately define the anatomic stage. Understanding the advantages and disadvantages of available methods for staging lung cancer is critical to clinician decision making. In patients with lung cancer without distant metastases, the staging of mediastinal lymph nodes determines treatment options. To minimize the risk and cost, the most appropriate method of staging should identify the highest disease stage while carrying acceptable risk. Minimally invasive endoscopic needle techniques to stage the mediastinum are the first choice to assess for metastases in accessible lymph node stations. Surgical techniques are generally reserved for specific clinical situations, including following negative endoscopic needle techniques when suspicion for nodal involvement is high and to assess endoscopically inaccessible lymph nodes. This review provides a concise account of TNM staging of non-small cell lung cancer (NSCLC) and overview of procedures available for the staging of lung cancer.

Journal of Respiration doi: 10.3390/jor4010004

Authors: Michael Gioia Rosa L. Arancibia

Pleural effusion is the most common disease among all pleural diseases and affects 1.5 million patients per year in the United States. Different interventions can be performed when dealing with pleural effusions. In this review, we present medical thoracoscopy as a minimally invasive procedure with both diagnostic and therapeutic utility in the management of pleural disease. It has a higher diagnostic yield than commonly performed percutaneous procedures (thoracentesis, closed pleural biopsy) and simultaneously offers many of the therapeutic benefits of more invasive procedures, such as video-assisted thoracoscopic surgery, with a lower risk profile. The role of medical thoracoscopy is evolving and will likely continue to expand as more centers start performing the procedure nationwide.

Journal of Respiration doi: 10.3390/jor4010003

Authors: Aristides J. Armas Villalba Bruce F. Sabath

Thermal ablative techniques are part of the armamentarium of interventional pulmonologists for the treatment of a diverse range of pathologies, but most importantly used in airway obstruction and airway bleeding. These techniques can be categorized based on their onset of action into rapid and delayed ablative methods. Understanding the nuances of each technique is essential, as most clinical scenarios demand a combination of modalities, commonly referred to as a “multi-modality approach”. This comprehensive review aims to elucidate the fundamental principles of rapid ablative techniques, including laser therapy, argon plasma coagulation (APC), and electrocautery, along with the research that underpins their clinical application.

Journal of Respiration doi: 10.3390/jor4010002

Authors: Abdelbassat Ketfi Fayçal Selatni Cherifa Djouadi Rama Touahri

Introduction: There are a limited number of epidemiological studies describing the global burden of chronic diffuse interstitial lung diseases (ILD) and their subtypes’ heterogeneity worldwide. Our main is to characterize new-onset ILDs in Algeria and compare our results with data from other populations. Materials and Methods: Newly diagnosed ILDs were prospectively collected in a single-center observational cohort study including all patients diagnosed as ILDs in the pulmonology, phthisiology, and allergology departments between 2015 and 2019. Detailed anamnestic and clinical data were collected at the time of diagnosis. The results of high-resolution computed tomography (HRCT), serological tests, biology data, and respiratory functional exploration were systematically performed and collected. Results: A total of 455 cases were included. The mean age was 59.4 ± 13.2 years. There was a slight predominance of females (300; 65.9%). The most common disease was ILD secondary to connective tissue disease (CTD) or ILD-CTD (48.1%), followed by idiopathic interstitial pneumonias (IIPs) (23.5%), sarcoidosis (16.9%), interstitial pneumonia with autoimmune features (IPAF) (12.1%), and hypersensitivity pneumonitis (HP) (2.4%). Idiopathic pulmonary fibrosis (IPF) was present in 8.6% and unclassifiable ILD in 4.6% of the total ILD cases. Conclusions: ILD-CTD, IIP, and sarcoidosis were the most frequently observed ILDs in this Algerian population. Similarities and many differences were found compared to previous data from other countries.

Journal of Respiration doi: 10.3390/jor4010001

Authors: Sean Duenas Juliana Derfel Margaret Gorlin Serena Romano Wei Huang Alex Smith Javier Ticona Cristina Sison Martin Lesser Linda Shore-Lesserson Negin Hajizadeh Janice Wang

Hypercoagulability in COVID-19 patients was associated with increased mortality risk during the pandemic. This retrospective, observational study investigated whether the use of a thromboelastography (TEG)-guided anticoagulation protocol could decrease death and bleeding in critically ill COVID-19 patients. A TEG-guided protocol was instituted in one of two intensive care units. Primary outcomes of composite scores were the following: (0) major bleed and death; (1) death without major bleed; (2) major bleed without death; and (3) no bleed or death. Out of 134 patients, 67 in the TEG group were propensity matched to 67 in the comparator group based on age, gender, body mass index, presence of chronic kidney disease, cardiovascular disease, diabetes, and duration of non-invasive ventilation. There were no significant differences in rates of composite outcomes of bleeding or death in patients managed with or without a TEG-guided protocol (p = 0.22, Bowker symmetry testing). Out of the 67 patients in the TEG group, the TEG protocol led to anticoagulation change in 26 patients. Death was lower in this TEG-changed group (54%) compared to the comparator group (81%), although not significant (p = 0.07). TEG-guided protocol use did not reduce composite outcomes of death and bleeding, Future studies may further elucidate potential benefits.

Journal of Respiration doi: 10.3390/jor3040022

Authors: Mohamed Talaat Xiuhua Si Jinxiang Xi

In this study, we present a novel approach to differentiate normal and diseased lungs based on exhaled flows from 3D-printed lung models simulating normal and asthmatic conditions. By leveraging the sequential learning capacity of the Long Short-Term Memory (LSTM) network and the automatic feature extraction of convolutional neural networks (CNN), we evaluated the feasibility of the automatic detection and staging of asthmatic airway constrictions. Two asthmatic lung models (D1, D2) with increasing levels of severity were generated by decreasing the bronchiolar calibers in the right upper lobe of a normal lung (D0). Expiratory flows were recorded in the mid-sagittal plane using a high-speed camera at 1500 fps. In addition to the baseline flow rate (20 L/min) with which the networks were trained and verified, two additional flow rates (15 L/min and 10 L/min) were considered to evaluate the network’s robustness to flow deviations. Distinct flow patterns and vortex dynamics were observed among the three disease states (D0, D1, D2) and across the three flow rates. The AlexNet-LSTM network proved to be robust, maintaining perfect performance in the three-class classification when the flow deviated from the recommendation by 25%, and still performed reasonably (72.8% accuracy) despite a 50% flow deviation. The GoogleNet-LSTM network also showed satisfactory performance (91.5% accuracy) at a 25% flow deviation but exhibited low performance (57.7% accuracy) when the deviation was 50%. Considering the sequential learning effects in this classification task, video classifications only slightly outperformed those using still images (i.e., 3–6%). The occlusion sensitivity analyses showed distinct heat maps specific to the disease state.

Journal of Respiration doi: 10.3390/jor3040021

Authors: Keigo Kobayashi

The discovery of the efficacy of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients has revolutionized lung cancer therapy. Although almost all responders acquire drug resistance within a few years, many studies have revealed several acquired-resistant mechanisms and developed therapeutic strategies countervailing them, most notably against the EGFR T790M gatekeeper mutation. However, little progress has been made in terms of elucidating the mechanisms of primary resistance. Primary resistance may be defined into two types of resistance, clinically representing patients that do not respond (non-responders) to EGFR-TKIs. The first group consists of approximately 10% of patients that are insensitive to EGFR-TKIs from the outset (intrinsic primary resistance), and 20–30% of the second group consists of patients that seem to clinically benefit at first, but experience early relapse within six months (late primary resistance). In this review, we first provide an overview of drug-induced lung cancer dynamics. We then delve into the mechanisms of primary resistance, with a primary focus on two specific subtypes of resistance. We suggest that “intrinsic primary resistance” is characterized by pre-existing somatic and genomic changes and cell of origins, while “late primary resistance” is correlated with the drug-tolerant persister state. Developing therapeutic strategies to overcome primary resistance is crucial to prolonging the duration of EGFR-TKI therapy. Ultimately, this will allow for an enhanced understanding of lung cancer’s evolutional process, leading to the reversal of acquired resistance and the complete eradication of lung cancer.

Journal of Respiration doi: 10.3390/jor3040020

Authors: Michael J. Nicholson Christopher Manley Danish Ahmad

Thoracentesis is a fundamental procedure in interventional pulmonology, providing both diagnostic and therapeutic value. This review article offers a comprehensive analysis of thoracentesis, delving into pleural anatomy, procedural techniques, indications, and recent advancements. The article details the evolution of thoracentesis, including the crucial role of ultrasound guidance and emerging approaches that enhance precision and minimize complications. It addresses the wide range of indications for thoracentesis in diverse clinical scenarios, from the diagnosis of pleural effusions to therapeutic drainage of pleural collections. Furthermore, this review explores the management of coagulopathy and anticoagulation pertaining to thoracentesis. It will also provide strategies for preventing and managing complications, ensuring that thoracentesis remains a well-tolerated procedure with minimal risks. This article concludes by examining future directions in thoracentesis, including potential innovations and trends that will shape the landscape of interventional pulmonary medicine. This review serves as an essential resource for pulmonologists, interventional radiologists, and healthcare professionals, offering a comprehensive update on thoracentesis.

Journal of Respiration doi: 10.3390/jor3040019

Authors: Aulia Rahman Ardan Fariz Nurwidya

Interstitial lung disease (ILD), which is characterized by pulmonary fibrosis, is a diverse group of disorders. Nintedanib, an antifibrotic drug, is known to attenuate disease progression in ILD with progressive fibrosis, but its efficacy in autoimmune-disease-related ILD remains uncertain. We conducted a comprehensive search for relevant randomized controlled trials, systematic reviews and meta-analyses included in PubMed, ScienceDirect and Scopus databases as of 23 June 2022 and manually reviewed reference lists. Among the 689 titles and abstracts screened, 24 studies were considered, with 4 randomized controlled trials included in our review. Nintedanib, administered at 150 mg twice daily for 52 weeks, consistently slowed forced vital capacity decline. Enhanced efficacy was observed when combining nintedanib with immunomodulators, and the most common adverse effect was diarrhea. In conclusion, our study suggests that nintedanib is a safe option for mitigating the progression of autoimmune-disease-related ILD, providing valuable insights into its potential therapeutic role in this context.

Journal of Respiration doi: 10.3390/jor3040018

Authors: Driscoll DeVaul Britney Reulet Jacob Daniels Xiaoqian Zhu Renee Wilkins Xiaoshan Z. Gordy

The COVID-19 pandemic had an immense effect on the well-being of healthcare professionals. In this study, researchers utilized a quantitative cross-sectional study design to investigate the degree of compassion satisfaction and fatigue amongst respiratory therapists in the state of Mississippi as a result of providing care to patients during the COVID-19 pandemic. Quantitative data were collected using an anonymous online survey that assessed the well-being and satisfaction of licensed respiratory therapists in the state of Mississippi. More specially, survey responses (n = 326) were quantitatively evaluated to measure the association between demographic variables and compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS). Ninety-seven percent of participants reported a medium to high CS level, while 74% indicated having a medium to high level of BO, and 69% reported a medium to high level of STS. Neither age nor gender had a significant difference in CS (p = 0.504; p = 0.405), BO (p = 0.161; p = 0.285), or STS (p = 0.145; p = 0.252). Those working for more than 10 years at their current employer had higher CS (M = 38.7) and lower BO (M = 24.9) and STS (M = 24.8) scores. The number of hours worked, specifically overtime, had a significant impact on BO (β = 0.09, p = 0.028) and STS (β = 0.0.11, p = 0.019), but not CS (β = 0.02, p = 0.655). These findings suggest that the number of years employed in the field impacts the level of compassion satisfaction and contributes to lower levels of burnout and secondary traumatic stress. The age of a patient may also affect levels of compassion and burnout. The results of this study highlight the importance of developing incentive plans in an effort to retain employees.

Journal of Respiration doi: 10.3390/jor3040017

Authors: Giovanna Elisiana Carpagnano Vitaliano Nicola Quaranta Claudia Crimi Pierachille Santus Francesco Menzella Corrado Pelaia Giulia Scioscia Cristiano Caruso Elena Bargagli Nicola Scichilone Eva Polverino

Introduction: Asthma and bronchiectasis are often partners in a complex but uneven relationship with asthma receiving more attention. The aim of this study is to describe how bronchiectasis is investigated in some Severe Asthma (SA) Centers, scattered throughout the Italian territory. Materials and Methods: We enrolled 92 patients with SA and bronchiectasis from eight Italian SA Centers and recorded diagnostic approaches to investigate SA and bronchiectasis at the time of enrollment (T0), at the 6-month (T1), and at the 12-month (T2) follow-up visits. Results: A statistically significant heterogeneous diagnostic approach emerged across the centers under study. In fact, while, as expected, all involved centers made an in-depth investigation of SA, only a few of them provided a complete investigation of bronchiectasis in order to provide specific treatment. Discussion: This real-life multicenter study confirmed that patients with coexistent SA and bronchiectasis are mainly investigated for pheno-endotyping asthma but rarely for the complete assessment of bronchiectasis. We believe that the diagnostic flowchart of SA patients with suspicion or confirmed bronchiectasis needs to be clarified and implemented as the association of these conditions strongly influences the final outcome and management of these patients.

Journal of Respiration doi: 10.3390/jor3040016

Authors: Mengli Zhong Muhan Zou Yue Yao Hao Wu Weiwei Su Yonggang Wang Peibo Li

Cigarette combustion has the potential to generate over 7000 chemicals, the majority of which are reactive free radicals that are known to trigger pro-inflammatory and carcinogenic responses. Numerous contemporary investigations have proposed that the pathophysiological and cellular mechanisms underlying the release of extracellular vesicles (EVs) in response to cigarette smoke (CS) may serve as potential pathways for CS-induced pathogenesis, while also reflecting the physiological state of the originating cells. This review provides a concise overview of the pathophysiological mechanisms linked to CS-induced EVs in various lung diseases, including chronic obstructive pulmonary disease, lung cancer, pulmonary fibrosis, and pulmonary hypertension. Additionally, it explores the potential and prospects of EVs as diagnostic biomarkers for CS-related lung diseases.

Journal of Respiration doi: 10.3390/jor3030015

Authors: Jessica U. Damian Takalani G. Tshitangano

The coronavirus (COVID-19) pandemic caused sicknesses ranging from mild to deadly, which disrupted lives and healthcare systems across the globe. Despite the availability of vaccines that are effective in significantly reducing the risks of death and severe disease, misperceptions of COVID-19 vaccine safety, efficacy, risks, and mistrust in institutions responsible for vaccination campaigns have been reported as factors contributing to vaccine hesitancy, leading to an unsatisfactory vaccination rate, which resulted in some countries implementing mandatory COVID-19 vaccination to increase vaccine uptake. This scoping review aimed at mapping global countries that have adopted mandatory COVID-19 vaccination and the reaction of citizens. PRISMA Extension for Scoping Reviews was used. Google Scholar was used to identify papers published in English from December 2019 to February 2022, irrespective of their methodology. A total of 140 studies were identified. After screening for duplication, access, and relevance, 24 were eligible for review. Approximately eleven countries implemented mandatory vaccination, mostly among healthcare workers. Citizens’ reactions towards the policy varied, with some in support of the policy but with a preference for the healthcare workers, and some in support but with the condition that it will only apply to travel, schools, and shopping areas, while others rejected the policy. Studies that may be relevant but were excluded due to eligibility criteria may be a limiting factor to this study. Several ethical considerations should be explicitly addressed when evaluating whether mandatory COVID-19 vaccination is an ethically justifiable policy option as recommended by the WHO policy brief.

Journal of Respiration doi: 10.3390/jor3030014

Authors: Joseph Neluheni Joseph M. Mundadi Takalani R. Luhalima Thivhulawi Malwela

Background: TB is a significant public health problem around the world, with South Africa being one of the 30 high-burden TB countries, accounting for 87 percent of all estimated incident TB cases. In South Africa, which accounts for 3% of all instances worldwide, research on students’ experiences and understanding of underlying factors is lacking. These future leaders are still in a key time of physical and psychological development. This study aimed to test students’ understanding of pulmonary tuberculosis (PTB) and its causes at a rural institution of higher learning. Methodology: Quantitative method was used using a cross-sectional design. The study was conducted in the 2020 Vhembe District, Limpopo, South Africa. In the poll, 199 students living in overcrowded campus housing were interviewed. A self-administered questionnaire was used to collect data at the Thohoyandou campus. Data were analysed using version 26.0 of the Statistical Package for Social Sciences (SPSS), with a Spearman’s rank-order correlation run. Results: The findings of this study revealed that 25.6 percent of male students and 74.4 percent of female students, respectively, understood PTB, while students at the selected tertiary institution have insufficient awareness of the causes of PTB. The association between education and TB knowledge among the respondents was determined using Spearman’s rank-order correlation. There was a statistically significant positive association between education and TB knowledge (Spearman’s rho = 0.669, p = 0.035). Conclusions: The study found that students at a higher education institution lacked sufficient general Knowledge regarding PTB. PTB control measures should be adopted to implement better the NSP, NDP, Global STOP TB strategy and the SDGs.

Journal of Respiration doi: 10.3390/jor3030013

Authors: Jhonatan Betancourt-Peña Juan Carlos Ávila-Valencia Jenifer Rodríguez-Castro

Background: Pulmonary rehabilitation (PR) allows for the treatment of patients with chronic obstructive pulmonary disease (COPD) as an intervention strategy that improves functional capacity, dyspnea, and health-related quality of life. However, adherence to such programs might be improved. This study aimed to describe the differences in sociodemographic and clinical variables, functional capacity, and health-related quality of life in patients diagnosed with COPD adherent and non-adherent to pulmonary rehabilitation at a clinic in Cali, Colombia. Methods: This study followed a descriptive cross-sectional model with 150 patients diagnosed with COPD. Adherence was classified by taking into account the number of sessions completed: low (<35%), moderate (35–85%), and high (>85%). Sociodemographic, clinical, functional capacity, and health-related quality of life variables were considered. Results: Adherence to the PR was rated as high in 57.3% of patients. Variables such as sex, health system affiliation, height, functional capacity, resting SaO2, and health-related quality of life presented significant differences (p-value ≤ 0.05). The main causes of non-adherence to the program were medical recommendations that prevented continuing in the program due to clinical and safety issues and economic issues that prevented reaching the rehabilitation site, as it was unaffordable. Conclusions: It can be concluded that adherence to pulmonary rehabilitation was rated as high in 57.3% of patients. The high adherence to the PR program occurred in male patients with a capacity to pay the Colombian health system (contributory regime).

Journal of Respiration doi: 10.3390/jor3030012

Authors: Bektas Murat Yalcin Tugba Kertmen Muge Ustaoglu

Objective: This research aimed to determine the smoking frequency and smoking-related gestational and postpartum health problems in our study population. We investigated the quit rate during pregnancy and relapse after giving birth. The study was conducted in two university family health centers. A total of 270 women aged 18–45 with children were included in the study. Following receipt of verbal consent, the cases’ demographic data, previous obstetric information, smoking status, and gestational weight gain (GWG) were collected through face-to-face interviews and electronic records. The participants’ mean age was 35.75 ± 6.9 years and 28.1% were current smokers. Forty-one participants (16%) smoked during pregnancy, while the secondhand smoking rate was 30%. Ex-smokers experienced greater GWG (17.5 ± 1.7 kg (p = 0.003)) than current smokers and non-smokers. Small gestational age (SGA) and health problems in the first year of life were more frequent in the babies of smoker mothers (p < 0.05). The relapse rate was 81.4%, and the mean relapse interval was 13.9 ± 1.85 months. Having a smoker spouse (0.42 Exp(B), p = 0.035) and high GWG (0.98 Exp(B), p = 0.01) were identified as independent risk factors for relapse. Our results indicate that many of the smoker women quit during pregnancy. Special interventions may increase the quitting rate in pregnancy and reduce the subsequent relapse rate.

Journal of Respiration doi: 10.3390/jor3020011

Authors: Larisa D. Kiryukhina Elena V. Kokorina Pavel V. Gavrilov Nina V. Denisova Liudmila I. Archakova Petr K. Yablonskiy

Tuberculosis-related lung damage is very different. Lung ventilation disorders have been studied in patients with pulmonary tuberculosis (TB) during the active process and after treatment, but the main causes of gas exchange changes have not been sufficiently studied. Investigation of diffusing lung capacity in combination with bodyplethysmography is useful for the interpretation of pulmonary gas exchange disorders. The aim was to determine the relationship of gas exchange with the value of alveolar volume (VA) and pulmonary poorly communicating fraction (PCF) in patients with pulmonary TB. A total of 292 patients (117/175 M/W) with verified pulmonary TB with smoking age less than 10 packs-years underwent spirometry, bodyplethysmography, and DLCO by the single-breath method. PCF was estimated calculating the difference between total lung capacity (TLC) and VA (% TLC). Patients with low DLCO had statistically significantly lower spirometric values (FVC, FEV1, FEV1/FVC, MMEF), lower TLC, higher airway resistance, RV/TLC, air-trapping volume, and PCF. The patients with low level of DLCO were divided into four groups depending on level VA and PCF. In most patients with infiltrative tuberculosis (50%), the leading syndrome of the DLCO decrease was alveolar-capillary damage. In patients with tuberculomas, the syndromes of alveolar capillary damage and pulmonary ventilation inhomogeneity were with the same frequency (43%). In patients with disseminated tuberculosis, the most frequent syndrome of the DLCO decrease was pulmonary ventilation inhomogeneity (33%), then alveolar-capillary damage (29%) and mixed (24%). In patients with cavernous tuberculosis, the leading syndrome of the DLCO decrease was mixed (39%), then alveolar capillary damage (25%) and pulmonary ventilation inhomogeneity (23%). The syndrome of gas exchange surface reduction in patients with disseminated and cavernous tuberculosis was less common (14%). In conclusion, an additional evaluation of the combination of PCF and VA increases the amount of clinical information obtained using the diffusion lung capacity measurements, since it allows identifying various syndromes of gas exchange impairment. The leading causes of diffusing capacity impairment vary by different types of pulmonary TB.

Journal of Respiration doi: 10.3390/jor3020010

Authors: Xinhang Tu Nahar Saleh Raymond Young

Before the widespread use of antibiotics, purulent pericarditis was not uncommon and was predominantly a complication of bacterial pneumonia. We present a rare case of Escherichia coli (E. coli) purulent pericarditis without a clear source after a recent COVID-19 infection. Background: COVID-19 has been affecting millions of people worldwide since the outbreak in December 2019, and its involvement in multiple organ systems has been observed and studied. Multiple cardiac complications have been reported, most significantly the virus’ ability to induce acute coronary syndrome and myocarditis. Pericardial disease has also been reported but less frequently. COVID-19 infection is associated with a higher risk of secondary bacterial infection, but it is rare to see purulent pericarditis in the setting of a recent COVID-19 infection. Objective: Our case report depicts a patient who developed E. coli purulent pericarditis in the setting of a recent COVID-19 infection. It indicates a possible association between COVID-19 infection with dysregulation of the immune system.

Journal of Respiration doi: 10.3390/jor3020009

Authors: Howard Yu Sahil Zaveri Meshach Pillai Harsha Taluru Michael Schaible Sahil Chaddha Asad Ahmed Said Tfaili Patrick Geraghty

Leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is highly expressed throughout the body in multiple tissues and cell types. LIF is primarily known to induce the differentiation of myeloid leukemia cells, but recent studies show that LIF has many other functions, including playing multiple roles in cancer and normal physiology. LIF expression is linked to cellular proliferation, metastasis, inflammation, and chemoresistance. LIF expression and secretion are triggered by many means and its downstream signaling can vary based on tissue types. Recent publications suggest that LIF may play a role in pulmonary diseases and its regulation is altered through external factors, such as cigarette smoke, inflammation stimuli, or infections. This review outlines the current knowledge of the function of LIF protein, mediators of LIF expression, receptors it interacts with, downstream LIF signaling, and possible pulmonary outcomes mediated by LIF.

Journal of Respiration doi: 10.3390/jor3020008

Authors: Xiaoliang Wang Zachary Wright Jiayan Wang Gengqing Song

Patients with obstructive sleep apnea (OSA) commonly report gastroesophageal reflux disease (GERD) symptoms, and limited data suggest a relationship between OSA and GERD-related complications. To investigate this association, we performed a population-based analysis using National Inpatient Sample (NIS) data for 7,159,694 patients. After adjusting for risk factors, OSA patients had a significantly higher incidence of GERD (32.3%) compared to those without OSA (15.0%, p < 0.01). OSA patients also had a higher risk of developing GERD-related complications, including non-erosive esophagitis, erosive esophagitis, esophageal stricture, and Barrett’s esophagus with and without dysplasia. Therefore, our results emphasize the importance of early detection and management of GERD and its complications in patients with OSA, particularly those with additional risk factors such as obesity and smoking.

Journal of Respiration doi: 10.3390/jor3020007

Authors: Ashley Garcia Prakash V. A. K. Ramdass Maria E. Ramos-Nino

Background: Studies have shown an increased risk of asthma in patients with psoriasis and vice versa. Thus, we conducted a meta-analysis to estimate the pooled association between these two chronic inflammatory diseases. Methods: A systematic search of the literature was conducted through March 2023. Risk ratios (RRs) and prevalence were calculated. Results: A total of 11 studies comprising 110,978 patients with psoriasis and 1,898,071 controls were included in the first meta-analysis. The prevalence of asthma in patients with psoriasis was 9.2% (0.075, 0.110), and the pooled risk ratio (RR) was 1.43 (1.23,1.66). Subgroup analysis showed that older patients (≥50 years) have a higher pooled risk of asthma [RR 1.59 (1.41, 1.79)] than younger patients (20–49 years) [RR 1.23 (1.07,1.41)]. In addition, a significantly higher risk of asthma was seen in patients with moderate to severe psoriasis [RR 1.48 (1.17, 1.88)) when compared to their controls than those with mild psoriasis [RR 1.28 (1.14, 1.44)]. A total of 3 studies comprising 468,869 asthma patients and 11,063,349 control were included in the second meta-analysis. The prevalence of psoriasis in asthma patients was 1.3%, 0.004, 0.029), and the pooled risk ratio was 1.23 (1.02,1.47). Conclusions: This meta-analysis provides clear evidence for the bidirectional association between asthma and psoriasis.

Journal of Respiration doi: 10.3390/jor3020006

Authors: Akeza Awealom Asgedom

Workers who are working in dusty environments might be associated with respiratory health problems. In Ethiopia, factories processing wood, textile, coffee, flour, cement and other materials are associated with dust emission. Furthermore, despite the adoption of the International Labor Organization (ILO) convention, the available constitution and labor proclamation, there are a lot of gaps in terms of occupational health and safety measures in Ethiopia. The current review aims to examine the existing evidence, current challenges and future direction regarding dust exposure and respiratory health in selected Ethiopian factories. Searches of peer-reviewed articles with full-length papers were made in online databases such as PubMed, Web of Science, MEDLINE, EMBASE and Google Scholar with a key words “Dust exposure”, “Respiratory health”, “Respiratory symptom”, “Ethiopia” and “Factory workers” from January 2000 to March 2023. The review found that excessive dust exposure is associated with a high prevalence of respiratory health problems. Lack of personal protective equipment and absence of safety and health training were the main occupational health deficits identified in most factories. Actions that focus on these deficiencies are commendable. Interventions focused on safety and health trainings, and the provision of adequate personal protective equipment of the required quality is recommended. In addition, administrative solutions and longitudinal studies on dust exposure and respiratory health are suggested.

Journal of Respiration doi: 10.3390/jor3020005

Authors: Adhya Mehta Amrin Kharawala Sanjana Nagraj Samuel J. Apple Diego Barzallo Majd Al Deen Alhuarrat Cesar Joel Benites Moya Sindhu Vikash Panagiotis Zoumpourlis Sophia Xesfingi Dimitrios Varrias Yunus Emre Demirhan Leonidas Palaiodimos Dimitrios Karamanis

Hyperlipidemia has been associated with worse outcomes in patients with Coronavirus disease 2019 (COVID-19). However, lower LDL-C (low-density lipoprotein cholesterol) levels have been associated with increased COVID-19 severity and mortality. We conducted a retrospective observational study of patients with COVID-19 admitted to New York City Health and Hospitals from 1 March 2020 to 31 October 2020, comparing pre-COVID-19 LDL-C levels or LDL-C levels obtained during COVID-19 hospitalization, with the need for invasive mechanical ventilation and death. Propensity score matching was performed using logistic regression models, and standardized mean differences were calculated. A total of 3020 patients (median age 61 years; 36% women) were included. In the matched cohort, on multivariate logistic regression analysis, LDL was inversely associated with in-hospital death (OR: 0.99, 95% CI: 0.986–0.999, p = 0.036). As a categorical variable, LDL > 70 mg/dL was associated with 47% lower likelihood of invasive mechanical ventilation (OR: 0.53, 95% CI: 0.29–0.95, p = 0.034). No significant association between pre-COVID-19 LDL and death or invasive mechanical ventilation was found (OR: 1.00, 95% CI 0.99–1.01, p = 0.833). Low LDL-C level measured during COVID-19 was associated with a higher likelihood of invasive mechanical ventilation and in-hospital death. A similar association was not found between pre-COVID-19 LDL-C and these outcomes. LDL-C levels obtained during COVID-19 are likely not reflective of the baseline lipid profile.

Journal of Respiration doi: 10.3390/jor3010004

Authors: Ndidzulafhi Selina Raliphaswa Dorah Ursula Ramathuba Takalani Rhodah Luhalima Seani Adrinah Mulondo Thivhulawi Malwela Azwidihwi Rose Tshililo Julia Langanani Mafumo Maria Sonto Maputle Mary Maluleke Takalani Ellen Mbedzi Hilda Nwamuhohova Shilubane Nthomeni Dorah Ndou Khathutshelo Grace Netshisaulu Mutshinyalo Lizzy Netshikweta

Background: Effective communication between health care professionals, admitted patients, and their families is crucial to improving the health care outcomes and patient satisfaction. Hence, barriers to effective communication cause a lot of confusion, frustration, and misunderstanding. The study aimed to identify the perceived barriers to effective communication between patients, their families, and health care professionals during the COVID-19 pandemic in public hospitals in Limpopo Province. The study was conducted in rural areas of Vhembe District, Limpopo Province. Methodology: A qualitative exploratory descriptive method was adopted to explore and describe the barriers of effective communication among patients, relatives, and health care professionals during the COVID-19 pandemic in public hospitals in the Vhembe District. Eleven (11) participants were purposively selected. Unstructured in-depth individual interviews were used to collect data and analyzed using thematic analysis following Tesch’s eight steps. Results: The study findings revealed that there was ineffective communication by health care professionals. This was discussed under three themes that emerged: poor communication of diagnosis and prognosis and treatment outcomes; lack of accurate knowledge regarding the virus morphology, variant, and treatment protocols; and the inconsistencies in the dissemination of COVID-19 protocols. Conclusions: Full communication benefits both patients, relatives, and health care professionals as knowledge and understanding are enhanced through communication. Therefore, health care professionals should provide the patients and their relatives with full information about the disease and the visitation protocols to be followed. The study contribution was to explore barriers to effective communication to the patients and relatives by the health care professionals.

Journal of Respiration doi: 10.3390/jor3010003

Authors: Huanhuan Jiang Xiang Gao Yong Gao Yatao Liu

The E-cigarette has been promoted as an alternative nicotine delivery device with potentially fewer toxicant emissions. The objective of this review is to summarize the current knowledge on the particle size distribution (PSD) of e-cigarette emissions and to analyze the knowledge gaps between existing particle size measurements and the vision toward harm reduction from e-cigarette use. Here, we focus on firstly describing the physical parameters used to characterize PSD, followed by comparing particle size measurement approaches, investigating the factors that impact the PSD of e-cigarette mainstream aerosols, and conclude by linking size distribution to the respiratory dosimetry by demonstrating the modeling results of particle deposition in the respiratory tract. This review calls for a harmonized testing protocol to conduct inter-comparisons and further understand e-cigarette particle sizes. Among the influencing factors investigated, puff topography, operation power, flavorings, PG/VG ratio, and nicotine strength impose a substantial impact on the PSD, but the underlying mechanisms have not yet been fully investigated. The effects brought by the type of device refill and nicotine are yet inconclusive due to lack of evidence. Coil aging has no significant impact on the PSD of e-cigarette aerosols within the coil lifetime. Lastly, while computational models of particle deposition have been adopted to profile the deposition of e-cigarette mainstream emissions, existing models have limited applicability and generality when dealing with e-cigarette aerosols that have high volatility and hygroscopicity, which can dynamically evaporate or grow during the transport process. Additionally, the size-dependent chemical composition (e.g., nicotine and harmful and potentially harmful constituents) of e-cigarette aerosols is unknown, impeding the understanding of the health effects of e-cigarette use. Therefore, it is essential for future studies to bridge these knowledge gaps and unveil the mechanisms determining PSD and respiratory deposition.

Journal of Respiration doi: 10.3390/jor3010002

Authors: JoR Editorial Office JoR Editorial Office

High-quality academic publishing is built on rigorous peer review [...]

Journal of Respiration doi: 10.3390/jor3010001

Authors: Aman Nagar Shubhajeet Roy Jyoti Bajpai Ajay Verma Surya Kant

Aspergillus fumigatus can cause an immunological hypersensitivity reaction known as allergic bronchopulmonary aspergillosis (ABPA), which often worsens asthma and cystic fibrosis patients’ conditions. In India, where tuberculosis (TB) is endemic, a significant proportion of allergic bronchopulmonary aspergillosis (ABPA) patients are misdiagnosed as pulmonary TB before reaching a diagnosis of ABPA due to long-lasting symptoms. We discuss an uncommon presentation of ABPA with type II respiratory failure in a 48-year-old asthmatic female. Given this, one can speculate on the importance of ABPA presenting with respiratory failure since these cases are rare and diagnosed quite late, which can also prove fatal.

Journal of Respiration doi: 10.3390/jor2040015

Authors: Xiuhua April Si Jinxiang Xi

Pulmonary gas exchanges are vital to human health, and disruptions to this process have been associated with many respiratory diseases. Previous gas exchange studies have predominately relied on whole-body testing and theoretical analysis with 1D or static models. However, pulmonary gas exchanges are inherently a dynamic process in 3D spaces with instantaneous interactions between air, blood, and tissue. This study aimed to develop a computational model for oxygen exchange that considered all factors mentioned above. Therefore, an integrated alveolus–membrane–capillary geometry was developed with prescribed rhythmic expansion/contraction. Airflow ventilation, blood perfusion, and oxygen diffusion were simulated using COMSOL. The temporal and spatial distribution of blood flow and oxygen within the capillaries were simulated under varying breathing depths and cardiac outputs. The results showed highly nonuniform blood flow distributions in the capillary network, while the rhythmic oscillation further increased this nonuniformity, leading to stagnant blood flow in the distal vessels. A static alveolus–capillary geometry underestimated perfusion by 11% for normal respirations, and the deviation grew with breathing depth. The rhythmic motion caused a phase lag in the blood flow. The blood PO2 reached equilibrium with the alveolar air after traveling 1/5–1/3 of the capillary network. The time to reach this equilibrium was significantly influenced by the air–blood barrier diffusivity, while it was only slightly affected by the perfusion rate. The computational platform in this study could be instrumental in obtaining refined knowledge of pulmonary O2 exchanges.

Journal of Respiration doi: 10.3390/jor2040014

Authors: Cesar Moran

The launching of a new journal is always complicated for many factors, mainly when the journal has special focus [...]

Journal of Respiration doi: 10.3390/jor2030013

Authors: Peter M. Mphekgwana Sogo F. Matlala Takalani G. Tshitangano Naledzani J. Ramalivhana Musa E. Sono-Setati

The coronavirus disease (COVID-19) pandemic has recently impacted and destabilised the global community. The healthcare systems of many countries have been reported to be partially or entirely interrupted. More than half of the countries surveyed (53%) have partially or completely disrupted hypertension treatment services. A population-based retrospective cohort study approach was used to determine the prevalence of hypertension and related risk factors for mortality in COVID-19 hospitalised patients in the Limpopo Province, South Africa. Hierarchical logistic regression was applied to determine the determinants of hypertension. Sixty-nine percent (69%) of mortality among individuals with laboratory-confirmed SARS-CoV-2 were elderly persons aged 60 years and above admitted to a person under investigation (PUI) ward (52%), and 66% had hypertension. Among the hospitalised COVID-19 patients who died, prominent risk factors for hypertension were advanced age, the presence of co-morbidities, such as diabetes and HIV/AIDS. There was no evidence to establish a link between hypertension and COVID-19 case severity. More cohort and systematic studies are needed to determine whether there is a link between hypertension and COVID-19 case severity.

Journal of Respiration doi: 10.3390/jor2030012

Authors: Marco Marando Adriana Tamburello Jens P. Diedrich Antonio Valenti Pietro Gianella

Albeit inhalation therapy is the cornerstone in chronic obstructive pulmonary disease (COPD) treatment, inhaler technique is rarely evaluated, and training materials are often insufficient. In this single-center study, we aimed to evaluate the effectiveness of a teaching session complemented by a flyer on inhaler technique in COPD patients and to evaluate the perceived quality of the flyer. A total of 30 participants with stable COPD who had never used a soft mist inhaler before (Respimat®, Boehringer Ingelheim) received a brief teaching session on proper inhaler technique complemented by a flyer (visit 1). The teaching intervention was completed by a pulmonologist. Epidemiological and clinical characteristics of COPD were collected by a questionnaire, and the ability to properly handle the inhaler was assessed. After 14 days, inhaler handling was re-evaluated, and patients were asked to rate the flyer (visit 2). After the initial training, proper inhaler handling was achieved in 80.0% of patients. Inhaler proficiency was maintained after 14 days (83.0% of the patients used the Respimat® correctly, p-value > 0.99). The flyer was considered at least good by 27 patients (90.0%). This study indicated that the administration of an educational intervention resulted in persistent good competence in inhaler technique at a 14-day follow-up.

Journal of Respiration doi: 10.3390/jor2030011

Authors: Leah Taylor Katherine Swainston Christopher Hurst Avinash Aujayeb Hannah Poulter Lorelle Dismore

Patients with mesothelioma (PwM) have a poor prognosis and are at risk of adverse health outcomes and poor health-related quality of life. Sarcopenia and malnutrition are important prognostic factors for cancer patients and can be partially reversed with adequate nutrition and physical activity/exercise. There is a limited evidence base about the nutritional status of PwM, the understanding of which might potentially influence interventions in PwM. The primary aim of the Help-Meso (Health and Lifestyle of PwM) study is to describe the nutrition, appetite, physical activity and attitude towards lifestyle interventions of PwM. Patients, informal carers and health professionals will be invited to participate in semi-structured interviews and thematic analysis will be performed. The secondary aim of Help-Meso is to assess the feasibility of nutritional screening of PwM via a validated quantitative tool (Malnutrition Universal Screening Tool). The findings from this study will provide an understanding of the health and lifestyle of PwM and the corresponding attitudes of their informal carers and healthcare providers. This information will inform the design of future targeted interventions to improve the nutrition, quality of life of PwM and outcomes. The study has Research Ethics Committee (REC) and Health Research Authority approvals obtained from Wales REC7 (Integrated Research Application System (IRAS) project ID 287193).

Journal of Respiration doi: 10.3390/jor2030010

Authors: Jaclyn Davis Pamela M. McMahon Emily Welch Cheryl McMahill-Walraven Aziza Jamal-Allial Tancy Zhang Christine Draper Anne Marie Kline Leslie Koerner Jeffrey S. Brown Melissa Van Dyke Ann Chen Wu

Introduction: Pediatric asthma affects 5.5 million US children and is the leading cause of pediatric chronic illness globally. Those with severe asthma have significantly higher healthcare costs compared to those with non-severe disease. Biologics are the newest class of anti-asthma therapy approved for use in patients with severe asthma > 6 years with the eosinophilic phenotype. Objective: The goals of this study were to (1) describe the baseline characteristics of new US pediatric mepolizumab users between 2015 and end dates that varied by data partner (6/30/19–5/31/21), (2) describe asthma medication use in the 12 months preceding and following mepolizumab initiation in this group and (3) assess adherence and persistence to mepolizumab in the 12 months following initiation. Methods: Through an observational cohort study using insurance claim databases, we studied children with a diagnosis of asthma in the preceding 12 months who started mepolizumab and had 12 months of follow-up data. Results: Baseline characteristics of the 72 children who initiated mepolizumab showed variable comorbidities, the most common being allergic rhinitis (88%) and recurrent respiratory infections (71%), as well as varied medication dispensings and patterns of healthcare utilization prior to initiating mepolizumab. Half met the criteria for severe asthma per the GINA guidelines. Comparing weighted averages of treatments dispensed in the 12 months prior to versus following mepolizumab initiation, we observed no significant change in asthma treatments dispensed. Conclusion: This study demonstrates that pediatric patients prescribed mepolizumab have variable previous treatment history and severity of disease, and we found no evidence that mepolizumab alters other asthma medications dispensed in the first 12 months following initiation.

Journal of Respiration doi: 10.3390/jor2020009

Authors: Takalani G. Tshitangano Musa E. Setati Peter M. Mphekgwana Naledzani J. Ramalivhana Sogo F. Matlala

More COVID-19 inpatient deaths occurred during the second wave when compared to the first wave in South Africa in both the public and private sectors. This study describes the characteristics of 969 COVID-19 inpatient deaths in the public sector of Limpopo Province during the first and second waves using population-based retrospective design. The results indicate that about 84% of deaths were aged 50+ years; 53.6% were females; 43% occurred in Capricorn district; 56% occurred in PUI wards; 64% had hypertension followed by diabetes mellitus; 88% manifested with shortness of breaths/respiratory distress on admission. The study concludes that as the average age among the population aged 60+ was greater among females than males, the increased death among females compared to males might be influenced by the older age of female inpatients during the first and second waves in Limpopo Province. Some COVID-19 inpatient deaths are possibly preventable if older women may be taken into consideration when planning prevention and management interventions in future pandemics.

Journal of Respiration doi: 10.3390/jor2020008

Authors: Masenyani Oupa Mbombi Livhuwani Muthelo Peter Mphekgwane Inos Dhau Joseph Tlouyamma Rathani Nemuramba Reneilwe Given Mashaba Katlego Mothapo Eric Maimela

Background: The primary purpose of introducing the COVID-19 vaccine was to fight the pandemic. However, the vaccine was not well received worldwide. This challenge has threatened the effective implementation and roll-out of COVID-19 immunization campaigns. The challenge of vaccine hesitancy was reported to be more prevalent in rural areas due to various factors such as cultural beliefs, misinformation, poverty, lack of education, and distrust of vaccines. Yet there seems to be a scarcity of studies determining the prevalence of vaccine hesitancy in deep rural areas of Limpopo. Purpose: The study aimed to explore the prevalence of COVID-19 hesitancy among the rural black population in South Africa. Study Methods: A longitudinal quantitative study was conducted with data from the DIMAMO Health and Demographic Surveillance Site (HDSS) database for 2020 to 2022. A non-probability total sampling technique was used to select the respondents. Trained fieldworkers collected data using an electronic data capture questionnaire. A comparison of categorical variables was performed using Chi-Square in SPSS version 26 and the statistical significance was set at p < 0.05, with a 95% confidence interval to analyze the data. Results: The limited availability of vaccination sites in Limpopo Province, South Africa, was associated with a reduced certainty that the vaccine would be accepted, as reported in the current study. The prevalence of visiting traditional healers was significantly higher in non-vaccinated than vaccinated participants among the rural black population, indicating a different cultural belief among the rural black population that existed before and during the COVID-19 pandemic. Conclusion: The present study findings show diverse factors of concern associated with vaccination hesitancy for COVID-19 among rural black people. Lack of education, gender, not being diagnosed with COVID-19, not being a Christian, visiting traditional healers, vaccine mistrust, unknown side effects, and a lack of confidence in the vaccine itself. Conspiracy theories were factors that impacted vaccine acceptance among black people living in rural areas. The prevalence of visiting traditional healers was significantly higher in non-vaccinated than vaccinated participants. Therefore, the present study findings emphasize the need to collectively integrate and utilize the traditional healers in the South African healthcare system.

Journal of Respiration doi: 10.3390/jor2020007

Authors: John Matthew Archer Jitesh Ahuja Chad D. Strange Girish S. Shroff Ebru Unlu Mylene T. Truong

Thin-section computed tomography (CT) has improved the detection of pericardial recesses and sinuses. Physiologic fluid in the pericardial recesses and sinuses can mimic mediastinal adenopathy. The misinterpretation of pericardial recesses and other benign pericardial entities in the oncologic setting can lead to inappropriate staging and management. Knowledge of the anatomy of the pericardium with emphasis on the imaging of different pericardial recesses on CT is important to avoid misdiagnosis, unnecessary further investigations, and/or biopsy.

Journal of Respiration doi: 10.3390/jor2020006

Authors: Peter M. Mphekgwana Musa E. Sono-Setati Abdul F. Maluleke Sogo F. Matlala

On 1 August 2020, South Africa’s Minister of Health announced that more than half of a million coronavirus cases were confirmed in the country. South Africa was by far the hardest-hit country in Africa, accounting for half of all infections reported across the continent. The prevalence of underlying conditions such as fever and blood oxygen saturation (SpO2) has been known known to be a significant determinant in the hospitalisation of COVID-19 patients. Low oxygen saturation on admission was reported as a strong predictor of in-hospital mortality in COVID-19 patients. The study sought to assess the association between body temperature and other clinical risk factors with low SpO2 among COVID-19 inpatient case fatalities. A quantitative retrospective study was carried out in Limpopo Province, employing secondary data from the Limpopo Department of Health (LDoH) on COVID-19 inpatients case fatalities across all districts in the province. The chi-square test and Pearson’s correlation coefficient were used to assess the relationship between body temperature and clinical risk factors with SpO2 levels. The findings of this paper indicated that age (older age), chills, sore throat, anosmia, dysgeusia, myalgia/body aches, diarrhoea and HIV/AIDS were associated with low SpO2 in-hospital mortality in COVID-19 patients. Nasal prongs and a face mask with a reservoir for respiratory support cannula were commonly used patient interfaces to provide supplemental oxygen, with the use of only a high-flow nasal cannula (HFNC) being minimal (7%). The majority of COVID-19 inpatient fatalities had normal body temperature (<38 °C) and SpO2, with no correlation between the two variables. Considering temperature screening as a possible strategy to combat the spread of COVID-19 or suspicious COVID-19 cases appeared, then, to be a pointless exercise. This study aimed to recommend new clinical criteria for detecting COVID-19 cases.

Journal of Respiration doi: 10.3390/jor2020005

Authors: Marco Mergiotti Alessandra Murabito Giulia Prono Alessandra Ghigo

Cystic fibrosis (CF), the most common genetic disease among the Caucasian population, is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR), a chloride epithelial channel whose dysfunction results in severe airway obstruction and inflammation, eventually leading to respiratory failure. The discovery of the CFTR gene in 1989 provided new insights into the basic genetic defect of CF and allowed the study of potential therapies targeting the aberrant protein. In recent years, the approval of “CFTR modulators”, the first molecules designed to selectively target the underlying molecular defects caused by specific CF-causing mutations, marked the beginning of a new era in CF treatment. These drugs have been demonstrated to significantly improve lung function and ameliorate the quality of life of many patients, especially those bearing the most common CFTR mutatant F508del. However, a substantial portion of CF subjects, accounting for ~20% of the European CF population, carry rare CFTR mutations and are still not eligible for CFTR modulator therapy, partly due to our limited understanding of the molecular defects associated with these genetic alterations. Thus, the implementation of models to study the phenotype of these rare CFTR mutations and their response to currently approved drugs, as well as to compounds under research and clinical development, is of key importance. The purpose of this review is to summarize the current knowledge on the potential of CFTR modulators in rescuing the function of rare CF-causing CFTR variants, focusing on both investigational and clinically approved molecules.

Journal of Respiration doi: 10.3390/jor2010004

Authors: Xiuhua Si Jensen S. Xi Mohamed Talaat Ramesh Donepudi Wei-Chung Su Jinxiang Xi

The use of impulse oscillometry (IOS) for lung function testing does not need patient cooperation and has gained increasing popularity among both young and senior populations, as well as in patients with breathing difficulties. However, studies of the IOS sensitivity to regional lung obstructions are limited and have shown mixed results. The objective of this study was to evaluate the performance of an IOS system in 3D-printed lung models with structural abnormalities at different locations and with different severities. Lung trees of two complexity levels were tested, with one extending to the sixth generation (G6) and the other to G12. The IOS responses to varying glottal apertures, carina ridge tumors, and segmental bronchial constrictions were quantified in the G6 lung geometry. Both the G6 and G12 lung casts were prepared using high-resolution 3D printers. Overall, IOS detected the progressive airway obstructions considered in this study. The resonant frequency dropped with increasing obstructions for all three disease phenotypes in the G6 lung models. R20Hz increased with the increase in airway obstructions. Specifically, R20Hz in the airway model with varying glottal apertures agreed reasonably well with complementary measurements using TSI VelociCalc. In contrast to the high-resistance (R) sensitivity to the frequency in G6 lung models, R was nearly independent of frequency in G12 lung models. IOS R20Hz demonstrated adequate sensitivity to the structural remodeling in the central airways. However, the changes of R5Hz and X5Hz vs. airway obstructions were inconclusive in this study, possibly due to the rigid lung casts and the difference of a container–syringe system from human lungs.

Journal of Respiration doi: 10.3390/jor2010003

Authors: Christy Lim Ronny Priefer

Asthma is a respiratory condition often stemming from childhood, characterized by difficulty breathing and/or chest tightness. Current treatment options for both adults and children include beta-2 agonists, inhaled corticosteroids (ICS), and leukotriene modifiers (LTM). Despite recommendations by the Global Initiative for Asthma, a substantial number of patients are unresponsive to treatment and unable to control symptoms. Pharmacogenomics have increasingly become the front line of precision medicine, especially with the recent use of candidate gene and genome- wide association studies (GWAS). Screening patients preemptively could likely decrease adverse events and therapeutic failure. However, research in asthma, specifically in pediatrics, has been low. Although numerous adult trials have evaluated the impact of pharmacogenomics and treatment response, the lack of evidence in children has hindered progress towards clinical application. This review aims to discuss the impact of genetic variability and response to asthmatic medications in the pediatric population.

Journal of Respiration doi: 10.3390/jor2010002

Authors: Odair Henrique Gaverio Diniz Monica Corso Pereira Silvia Maria Doria da Silva Marcel Koenigkam-Santos Ilma Aparecida Paschoal Marcos Mello Moreira

Background: In chronic obstructive pulmonary disease (COPD), morphological analysis made by computed tomography (CT) is usually correlated with spirometry as the main functional tool. In this study, quantitative CT analysis (QCT) was compared with volumetric capnography (VCap), alongside spirometry and the 6-min walk test (6MWT). Methods: Twenty-seven patients with severe/very severe COPD were included, compared with nineteen control subjects. All participants performed spirometry and chest high resolution CT scans that were analyzed with fully-automated software. The COPD group was also submitted to VCap and 6MWT. Results: COPD patients (65.07 ± 8.25 years) showed an average FEV1 of 1.2 L (44% of the predicted) and the control group (34.36 ± 8.78 years). VCap × QCT: positive correlations were observed with bronchial wall thickening and negative correlations with diameter and area of the bronchial lumen. Spirometry × QCT: positive correlations were observed between post-BD FVC, FEV1 and FEF 25–75% and diameter and luminal area of the airways and FVC and lung and vascular volumes (emphysema). Negative correlation was observed between post-BD FVC and FEV1 when compared with Pi10 (internal perimeter of 10 mm). 6MWT vs. QCT: negative correlations were observed between the distance covered with relative wall thickness (airways) and vascular volume and peripheral vascular volume (vasculature). Conclusion: Relevant correlations between QCT and pulmonary function variables were found, including the VCap, highlighting the importance of structural analysis in conjunction with a multidimensional functional assessment. This is the first study to correlate airway and parenchyma QCT with VCap.

Journal of Respiration doi: 10.3390/jor2010001

Authors: Muralidhar Aaina Kaliyaperumal Venkatesh Brammacharry Usharani Muthukumar Anbazhagi Gerard Rakesh Muthaiah Muthuraj

The present study aimed at analyzing the treatment outcomes and risk factors associated with fluoroquinolone drug resistance having mutations in the gyrA and gyrB genes. A total of 258 pulmonary tuberculosis samples with first-line drug-resistant (H, R, or HR) were subjected to GenoType MTBDRsl assay for the molecular detection of mutations. Among the 258 samples, 251 were drug-resistant tuberculosis and seven were sensitive to all first-line TB drugs. Out of 251 DR-TB cases, 42 cases were MDR TB, 200 were INH mono-resistant and nine cases were RIF mono-resistant tuberculosis. Out of 251 DR-TB cases performed with a MTBDRsl assay, 14 had Pre-XDR-FQ, one patient had pre-XDR-SLID, one had extensively drug-resistant tuberculosis (XDR-TB) and 235 cases were sensitive to both FQ and SLID drugs. The study group had a mean average of 42.7 ± 16.4 years. The overall successful treatment outcomes among the MDR, INH mono-resistant, and pre-XRD patients were 70.6%, 82.0%, and 51%, respectively. The percentage of risk for the unfavorable outcomes in the pre-XDR, INH -mono-resistant, and XDR cases were 113.84% increased risk with RR 2.14; 95% CI 0.7821–5.8468. The independent risk factor associated with the unfavorable outcomes to failure was 77.78% increased risk with RR 1.78; 95% CI 0.3375–9.3655. Logistic regression analysis revealed that the percentage relative risk among MDR-TB patients for gender, male (RR: 1.85), age ≥ 61 years (RR: 1.96), and diabetics (RR: 1.05) were 84.62%, 95.83%, and 4.76%, respectively. The independent risk factors associated with INH mono-resistant cases of age 16–60 (RR: 1.86), ≥61 year (RR: 1.18), and treated cases (RR: 5.06). This study presaged the significant risk of INH mono-resistant, pre-XDR, and MDR among males, young adults, diabetics, and patients with previous treatment failure. Timely identification of high-risk patients will give pronounced advantages to control drug resistance tuberculosis diseases.

Journal of Respiration doi: 10.3390/jor1040024

Authors: Priyanka Mishra Nikhil Pandey Ratna Pandey Yamini B Tripathi

Acute Respiratory Distress Syndrome is a familiar and destructive clinical condition characterized by progressive, swift and impaired pulmonary state. It leads to mortality if not managed in a timely manner. Recently the role of imbalanced macrophage polarization has been reported in ARDS. Macrophages are known for their heterogeneity and plasticity. Under different microenvironmental stimuli, they (M0) can switch between classically activated macrophage (M1) and alternatively activated (M2) states. This switch is regulated by several signaling pathways and epigenetic changes. In this review, the importance of macrophage M1 and M2 has been discussed in the arena of ARDS citing the phase-wise impact of macrophage polarization. This will provide a further understanding of the molecular mechanism involved in ARDS and will help in developing novel therapeutic targets. Various biomarkers that are currently used concerning this pathophysiological feature have also been summarized.

Journal of Respiration doi: 10.3390/jor1040023

Authors: Ranjeet Kumar Selvakumar Subbian

A granuloma, a pathologic hallmark of tuberculosis (TB), is a complex cellular structure that develops at the site of Mycobacterium tuberculosis (Mtb) infection and is comprised of different immune cell types. Severe pulmonary TB in humans is characterized by the presence of heterogeneous granulomas, ranging from highly cellular to solid/non-necrotic and necrotic lesions, within the lungs. The host-Mtb interactions within the granulomas dictate the containment of Mtb infection or its progression into a necrotic, cavitary disease. However, the immune environment in various granulomas is poorly understood. The myeloid-derived suppressor cells (MDSCs) are key immune cells that regulate the protective versus permissive host responses against Mtb infection. However, their contexture within the lung granulomas remains unclear. In this study, using single and multiplex immunohistochemical staining, we analyzed the distribution of MDSCs, macrophages, CD4+ T cells and their immunometabolic and effector function states in the solid/non-necrotic and necrotic granulomas in patients with active pulmonary TB. We found increased MDSCs with elevated expression of immunosuppressive molecules in the solid/non-necrotic granulomas. In contrast, cells in the solid and necrotic granulomas produced similar levels of IL-6 and IL-10. Our findings suggest that MDSCs are present in solid/non-necrotic granuloma, which may play an essential role in the progression into a necrotic lesion, thus exacerbating disease pathology and transmission.

Journal of Respiration doi: 10.3390/jor1040022

Authors: Onofrio Laselva Massimo Conese

Cystic fibrosis (CF) is an autosomal recessive multi-organ disease caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, with morbidity and mortality primacy related to the lung disease. The CFTR protein, a chloride/bicarbonate channel, is expressed at the apical side of airway epithelial cells and is mainly involved in appropriate ion and fluid transport across the epithelium. Although many animal and cellular models have been developed to study the pathophysiological consequences of the lack/dysfunction of CFTR, only the three-dimensional (3D) structures termed “spheroids” and “organoids” can enable the reconstruction of airway mucosa to model organ development, disease pathophysiology, and drug screening. Airway spheroids and organoids can be derived from different sources, including adult lungs and induced pluripotent stem cells (iPSCs), each with its advantages and limits. Here, we review the major features of airway spheroids and organoids, anticipating that their potential in the CF field has not been fully shown. Further work is mandatory to understand whether they can accomplish better outcomes than other culture conditions of airway epithelial cells for CF personalized therapies and tissue engineering aims.

Journal of Respiration doi: 10.3390/jor1040021

Authors: Rushikesh Deshpande Chunbin Zou

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the latest variant in the coronavirus family, causing COVID-19, has resulted in global pandemic since early 2020 leading to severe public health concern. So far, the pandemic has caused more than 200 million infections and 4 million deaths worldwide. Most of the studies are focused on developing prevention, intervention, and therapeutic strategies. However, underlying pathophysiology of the disease is important as well, which needs further attention. Cell death is one of the major causative mechanisms that leads to severe inflammation, and it is also an a posteriori consequence of the hyperinflammatory storm that renders poor prognosis of the disease. Substantial cell death has been reported in biopsy samples from post mortem patients. Among the distinct cell death pathways, apoptosis, the regulated programmed cell death plays an important role in the pathogenesis of the disease. Understanding the role of SARS-CoV-2 infection in apoptosis is critical to linearize the pathogenesis of the virus as well as the resultant disease, that may uncover novel therapeutic targets in treatment of COVID-19 patients. Here, we review the current progress on the underlying molecular mechanism(s) of SARS-CoV-2-induced apoptosis, not only at the level of the virus but also at its individual proteins.

Journal of Respiration doi: 10.3390/jor1030020

Authors: Abigail Reay Avinash Aujayeb Catherine Dotchin Ellen Tullo John Steer Katherine Swainston Lorelle Dismore

Introduction: Research into the long-term effects of coronavirus disease 2019 (COVID-19) continues at an unprecedented pace. Many physical long-term symptoms of COVID-19 have been reported and include headache, fatigue, muscle pain and breathlessness, etc. Psychological effects are not dissimilar to survivors of SARS. There is limited qualitative research exploring the mental health impacts and experiences of hospitalized COVID-19 inpatients. Methods: A prospective qualitative study is planned to explore patient experiences post hospital discharge following a diagnosis of COVID-19. The research aims to gain an understanding of how COVID-19 affects quality of life (QoL) and functional abilities. Patients discharged from the hospital will be invited to take part in semi-structured interviews discussing their experiences of hospitalization and the impact of COVID-19 on their QoL. Interviews will be conducted at three and six months following discharge from hospital. This study will provide important qualitative insight and may inform clinical interventions and commissioning decisions. Trial registration: The study has Research Ethics Committee (REC) and Health Research Authority (HRA) approvals obtained from Health and Care Research Wales (HCRW) [IRAS project ID 293196].

Journal of Respiration doi: 10.3390/jor1030019

Authors: Christopher S. Robinson Jennifer A. Wyderko Yeng Vang Galen Martin Robert T. Youker

Cystic Fibrosis (CF) is caused by loss of function mutations in the Cystic Fibrosis transmembrane conductance regulator (CFTR). The folding and assembly of CFTR is inefficient. Deletion of F508 in the first nucleotide binding domain (NBD1-ΔF508) further disrupts protein stability leading to endoplasmic reticulum retention and proteasomal degradation. Stabilization and prevention of NBD1-ΔF508 aggregation is critical to rescuing the folding and function of the entire CFTR channel. We report that the phenolic compounds Oleuropein and Hydroxytryosol reduce aggregation of NBD1-ΔF508. The NBD1-ΔF508 aggregate size was smaller in the presence of Hydroxytryosol as determined by dynamic light scattering. Neither phenolic compound increased the thermal stability of NBD1-ΔF508 as measured by differential scanning fluorimetry. Interestingly, Hydroxytyrosol inhibited the stabilizing effect of the indole compound BIA, a known stabilizer, on NBD1-ΔF508. Molecular docking studies predicted that Oleuropein preferred to bind in the F1-type core ATP-binding subdomain in NBD1. In contrast, Hydroxytyrosol preferred to bind in the α4/α5/α6 helical bundle of the ABCα subdomain of NBD1 next to the putative binding site for BIA. This result suggests that Hydroxytyrosol interferes with BIA binding, thus providing an explanation for the antagonistic effect on NBD1 stability upon incubation with both compounds. To our knowledge, these studies are the first to explore the effects of these two phenolic compounds on the aggregation and stability of NBD1-ΔF508 domain of CFTR.

Journal of Respiration doi: 10.3390/jor1030018

Authors: René D. ter Wee Bernardus J. Thio

High flow nasal cannula (HFNC) therapy is a non-invasive oxygen delivery mode which is safe and well tolerated by adults and children with respiratory distress. HFNC is increasingly used in children with respiratory distress due to mucus retention, such as bronchiolitis and acute asthma. However, he effectiveness of this therapy in acute asthma has not been well researched. To evaluate HFNC for acute childhood asthma, we designed a randomized prospective crossover trial. In the trial, children aged 6–18 years, with a forced expiratory volume in one second (FEV1) lability of ≥30% during an exercise challenge test (ECT) are included. The time of fully recovered lung function within 10% of the baseline after peak fall of FEV1 is compared with and without HFNC therapy. A 50% reduction of recovery time during HFNC therapy compared to recovery time without HFNC is considered clinically relevant, with a power of 80% and a significance level of 5%. Secondly, the pressure used by the HFNC device to deliver the constant present flow is evaluated. A relationship between the measured pressure and the degree of recovery may reveal a working mechanism behind HFNC.

Journal of Respiration doi: 10.3390/jor1030017

Authors: Warren Kindzierski Stanley Young Terry Meyer John Dunn

Background: An irreproducibility crisis currently afflicts a wide range of scientific disciplines, including public health and biomedical science. A study was undertaken to assess the reliability of a meta-analysis examining whether air quality components (carbon monoxide, particulate matter 10 µm and 2.5 µm (PM10 and PM2.5), sulfur dioxide, nitrogen dioxide and ozone) are risk factors for asthma exacerbation. Methods: The number of statistical tests and models were counted in 17 randomly selected base papers from 87 used in the meta-analysis. Confidence intervals from all 87 base papers were converted to p-values. p-value plots for each air component were constructed to evaluate the effect heterogeneity of the p-values. Results: The number of statistical tests possible in the 17 selected base papers was large, median = 15,360 (interquartile range = 1536–40,960), in comparison to results presented. Each p-value plot showed a two-component mixture with small p-values < 0.001 while other p-values appeared random (p-values > 0.05). Given potentially large numbers of statistical tests conducted in the 17 selected base papers, p-hacking cannot be ruled out as explanations for small p-values. Conclusions: Our interpretation of the meta-analysis is that random p-values indicating null associations are more plausible and the meta-analysis is unlikely to replicate in the absence of bias.

Journal of Respiration doi: 10.3390/jor1030016

Authors: Maria E. Ramos-Nino Charles D. MacLean Benjamin Littenberg

The association between obstructive lung disease and cardiovascular disease (CVD) has been suggested previously, but few studies have looked at this association in a diabetic cohort, a population highly susceptible to both comorbidities. A total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any obstructive lung disease. Laboratory data were obtained directly from the clinical laboratory. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between obstructive lung disease and CVD. In a multivariate logistic regression model, obstructive lung disease was significantly associated with CVD, even after correcting for potential confounders, including gender, obesity, low income, cigarette smoking, alcohol problems, and high comorbidity (odds ratio = 1.96; 95% confidence interval 1.37–2.81; p < 0.01). All components of CVD, including coronary artery disease (CAD), congestive heart failure (CHF), peripheral vascular disease (PVD), and cerebrovascular accidents (CVA), were also significantly associated with obstructive lung disease. These data suggest an association between obstructive lung disease and CVD in patients with diabetes. Future studies are needed to identify the mechanism supporting this association

Journal of Respiration doi: 10.3390/jor1020015

Authors: Radha Gopalaswamy V. N. Azger Dusthackeer Silambuchelvi Kannayan Selvakumar Subbian

Pathogenic Mycobacterium tuberculosis complex organisms (MTBC) primarily cause pulmonary tuberculosis (PTB); however, MTBC are also capable of causing disease in extrapulmonary (EP) organs, which pose a significant threat to human health worldwide. Extrapulmonary tuberculosis (EPTB) accounts for about 20–30% of all active TB cases and affects mainly children and adults with compromised immune systems. EPTB can occur through hematogenous, lymphatic, or localized bacillary dissemination from a primary source, such as PTB, and affects the brain, eye, mouth, tongue, lymph nodes of neck, spine, bones, muscles, skin, pleura, pericardium, gastrointestinal, peritoneum, and the genitourinary system as primary and/or disseminated disease. EPTB diagnosis involves clinical, radiological, microbiological, histopathological, biochemical/immunological, and molecular methods. However, only culture and molecular techniques are considered confirmatory to differentiate MTBC from any non-tuberculous mycobacteria (NTM) species. While EPTB due to MTBC responds to first-line anti-TB drugs (ATD), drug susceptibility profiling is an essential criterion for addressing drug-resistant EPTB cases (DR-EPTB). Besides antibiotics, adjuvant therapy with corticosteroids has also been used to treat specific EPTB cases. Occasionally, surgical intervention is recommended, mainly when organ damage is debilitating to the patient. Recent epidemiological studies show a striking increase in DR-EPTB cases ranging from 10–15% across various reports. As a neglected disease, significant developments in rapid and accurate diagnosis and better therapeutic interventions are urgently needed to control the emerging EPTB situation globally. In this review, we discuss the recent advances in the clinical diagnosis, treatment, and drug resistance of EPTB.

Journal of Respiration doi: 10.3390/jor1020014

Authors: Karl Jackson Opeyemi Kafi Dilraj S. Bhullar Jordan Scott Claire Storey Saara Hyatali Hannah Carlin Andrew Brown Emily Grimshaw Joseph Miller Hannah Rank Sean Porritt Michael Carling Avinash Aujayeb

Introduction: There are no prospective studies looking at complications of pleural procedures. Previous British Thoracic Society Pleural audits and retrospective case series inform current practice. Incidence of any complication is between 1–15%. We sought to add to the existing literature and inform local practice with regards to intercostal drains and thoracocenteses. Methods: Local Caldicott approval was sought for a review of all inpatient adult pleural procedures coded as ‘T122 drainage of pleural cavity’ and ‘T124 insertion of tube drain into pleural cavity’. Those undergoing thoracocentesis (all with a Rocket 6 Fg catheter) and intercostal drain insertion (ICD, all with Rocket 12 Fg drain) were identified. Continuous variables are presented as mean (±range) and categorical variables as percentages where appropriate. Results: 1159 procedures were identified. A total of 199 and 960 were done for pneumothorax and effusions respectively. Mean age was 68.1 years (18–97). There were 280 thoracocenteses and 879 ICDs. Bleeding occurred in 6 (0.5%), all ICDs (clotting and platelets were within normal range; one patient was on aspirin and one on aspirin and clopidogrel). All settled except for one who had intercostal artery rupture needing cardiothoracic intervention (no anti-coagulation). Nine pneumothoraces occurred (0.78%) in seven ICDs and two aspirations). There were three definite pleural space infections (0.3%) with three ICDs. Fall out rates for ICDs were 35 (3%). Nine were not sutured, and out of those, seven inserted in the Accident and Emergency department, out of hours. All others ‘came out’ due to patient factors (previous quoted rates up to 14%). Surgical emphysema occurred in 43 (41 ICDs), 3.7%. Eight were due to fall outs and three required surgical intervention. There was no re-expansion pulmonary oedema nor direct deaths. Conclusions: Complication rates of ICD and thoracocenteses are low. Checklists might help to remind operators of the need for suturing. Limitations of this study are its retrospective nature and reliance on correct hospital coding. We are currently contributing to a prospective observational study on pleural complications.

Journal of Respiration doi: 10.3390/jor1020013

Authors: Noheul Kim Ronny Priefer

Pneumonectomy is an entire lung removal and is indicated for both malignant and benign diseases. Due to its invasiveness and postoperative complications, pneumonectomy is still associated with high mortality and morbidity. Appropriate postoperative management is crucial in pneumonectomy patients to improve quality of life and overall survival rates. Diverse drug regimens are under development to be used in adjuvant chemotherapy or to improve respiratory health after a pneumonectomy. The most common causes for a pneumonectomy are non-small cell lung cancer, malignant pleural mesothelioma, and tuberculosis; thus, an appropriate drug regimen is necessary. The uncommon incidence of pneumonectomy cases remains the major obstacle in studies of postoperative drug regimens. As the majority of current studies include post-lobectomy and post-segmentectomy patients, it is highly recommended that further research of postoperative drug regimens be focused on post-pneumonectomy patients.

Journal of Respiration doi: 10.3390/jor1020012

Authors: Javier Enrique Fajardo-Rivero Melissa Mogollón Diego Fernando García-Bohórquez Andrés Villabona-Rueda Tania Mendoza-Herrera Alba Ramírez-Sarmiento Fabio Bolívar-Grimaldos Mauricio Orozco-Levi

Chronic thromboembolic disease (CTEPH) is one of the causes for developing pulmonary hypertension (PH). PH is characterized by an increase in pulmonary vascular pressure and resistance, ultimately leading to chronic overload. This study describes the clinical, functional, and hemodynamic characteristics as well as the established treatment strategy for a cohort of patients diagnosed with CTEPH in Bucaramanga, Colombia. In Colombia, PH is considered as an orphan disease with limited epidemiological data. We aim to provide useful information in order to help guide future clinical decisions for PH treatment and prevention. We conducted a cross-sectional study, obtaining clinical data from patients under follow-up, over 18 years of age, with hemodynamic confirmation of CTEPH in two pulmonary outpatient centers in Bucaramanga, Colombia between 2012 and 2018. 35 patients with diagnosis of CTEPH were included. Mean age was 52.3 ± 17.9 years. The mean time between the onset of symptoms to diagnosis was 14 months. 71% had a previous thrombotic event and 69% had functional class III and IV according to the world health organization (WHO) criteria. Most of the patients were classified as at high risk of mortality according to the European Society of Cardiology (ESC) and the European Respiratory Society (ERS/ESC) criteria and 60% were referred to undergo thromboendarterectomy. Most of the patients were under monotherapy treatment with Bosentan, the most prescribed medication in both monotherapy and dual therapy. This study identified a high number of patients in advanced stages of CETPH due to late diagnosis, related to health care limitations. This resulted in worse prognosis and quality of life. In addition, low adherence to non-pharmacological interventions was evidenced in patients who were not candidates for thromboendarterectomy despite the onset of pharmacological therapy.

Journal of Respiration doi: 10.3390/jor1020011

Authors: Avinash Aujayeb Donna Wakefield

Introduction: Cancer-related fatigue is well described. Fatigue in patients with a malignant pleural effusion (MPE) has not been directly studied. Methods: A prospective observational cohort pilot study ‘Do Interventions for Malignant Pleural Effusions (MPE) impact on patient reported fatigue levels (IMPE-F study)’ is planned to determine whether pleural interventions reduce fatigue in MPE. Fatigue will be assessed with a validated patient reported outcome measure, FACIT-F. Discussion: MPE-F has funding from Rocket Medical Plc, and is part of a Masters in Clinical Research at Newcastle University. Respondent fatigue will be addressed by the investigators going through the questionnaire with the participants. Inclusion criteria are all patients above 18 years of age with a presumed MPE undergoing a procedure and able to consent. The expected number of participants is 50. Trial registration: The IMPE-F study has Research Ethics Committee (REC) [20/YH/0224] and Health Research Authority (HRA) and Health and Care Research Wales (HCRW) approvals [IRAS project ID: 276451]. The study has been adopted on National Institute for Health Research portfolio [CPMS ID 46430].