Journal of Respiration

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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). Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article