Search Results (23)

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, characterized by chronic mucus hypersecretion (CMH) that exacerbates airway obstruction and accelerates disease progression. Effective airway clearance techniques are essential to improve respiratory function and reduce exacerbations. Temporary Positive Expiratory Pressure (T-PEP) is a novel airway clearance device that has shown promise in managing COPD. Objectives: This meta-analysis aimed to evaluate the efficacy of T-PEP in a standard pulmonary rehabilitation program. Methods: Following PRISMA guidelines, a comprehensive search of randomized controlled trials (RCTs) was conducted in the MEDLINE and PEDro databases. Data from 162 subjects, including those with severe COPD and bronchiectasis, were analyzed. Key outcomes assessed were changes in lung function (FVC, FEV1, TLC), inspiratory and expiratory pressures (MIP, MEP), gas exchange (PaO₂, PaCO₂), exercise capacity (6MWT), symptom severity (mMRC, CAT, BCSS), and exacerbation rates. Results: T-PEP significantly improved FVC, FEV1, TLC, MIP, MEP, and DLCO compared to baseline, with heterogeneity noted across studies. Improvements in gas exchange and physical capacity were observed, with PaO₂ increasing and PaCO₂ decreasing. T-PEP also reduced symptoms of cough and dyspnea, improving quality-of-life scores. Additionally, a notable reduction in acute exacerbations of COPD was seen after one month and three months of treatment. Conclusions: T-PEP therapy shows substantial benefits in improving lung function, exercise capacity, and quality of life while reducing exacerbation rates in COPD patients. Although promising, these findings require further confirmation through randomized clinical trials to establish the optimal application of T-PEP in various clinical settings and patient phenotypes. Full article

Background: Severe asthma is a challenging condition that often resists traditional treatments and requires high-dose inhaled corticosteroids and other controllers to manage uncontrolled symptoms. Recent advances include the use of biologic agents targeting specific inflammation pathways, which have improved symptom control and quality of life, although their effects on small airways remain less understood. Methods: This prospective observational study, conducted at Tor Vergata University Hospital in Rome from July 2021 to March 2024, aims to evaluate the efficacy of treatments in patients with uncontrolled severe asthma. It involves baseline assessments and follow-ups at 1 and 3 months post-biological therapy initiation, focusing on both spirometric and non-spirometric (oscillometry) measurements of the small airways to provide a comprehensive evaluation of respiratory function. Results: This study, conducted from July 2021 to March 2024, enrolled 40 patients with severe asthma, ultimately analyzing data from 31 participants who underwent biological therapy. The results showed significant improvements in asthma symptoms, the ACT scores increased significantly from visit 1 to visit 2 (p = 0.00008) and from visit 1 to visit 3 (p = 0.00047), and pulmonary function tests, with notable increases in FEV1 (from visit 1 (74.97 ± 23.43%) to visit 2 (82.96 ± 26.57%, p = 0.041) and to visit 3 (88.89 ± 31.41%, p = 0.003)) and quality of life scores, and substantial reductions in specific airway resistance and small airway dysfunction markers (the PEF, %pr post-BD showed significant improvement from visit 1 to visit 3 (p = 0.012)). However, oscillometric measurements showed no significant changes post-therapy. Conclusions: The study concluded that there was an improvement in the small airways measured by non-oscillometric values, without significant improvements in oscillometric parameters. Additionally, a significant improvement in symptoms was observed after the first month of therapy. There was also a significant increase in respiratory function after one to three months of therapy. Full article

Pulmonary function tests (PFTs) are pivotal in diagnosing and managing a broad spectrum of respiratory disorders. These tests provide critical insights into lung health, guiding diagnoses, assessing disease severity, and shaping patient management strategies. This review addresses the complexities and nuances inherent in interpreting PFT data, particularly in light of recent updates from the European Respiratory Society (ERS) and American Thoracic Society (ATS). These updates have refined interpretive strategies, moving away from definitive diagnostic uses of spirometry to a more probabilistic approach that better accounts for individual variability through the use of Z-scores and lower limits of normal (LLNs). Significantly, this narrative review delves into the philosophical shift in spirometry interpretation, highlighting the transition from direct clinical diagnostics to a more nuanced evaluation geared towards determining the likelihood of disease. It critiques the reliance on fixed ratios and emphasizes the need for reference values that consider demographic variables such as age, sex, height, and ethnicity, in line with the latest Global Lung Function Initiative (GLI) equations. Despite these advances, challenges remain in ensuring uniformity across different predictive models and reference equations, which can affect the accuracy and consistency of interpretations. This paper proposes a streamlined three-step framework for interpreting PFTs, aiming to unify and simplify the process to enhance clarity and reliability across various medical specialties. This approach not only aids in accurate patient assessments but also mitigates the potential for misdiagnosis and ensures more effective patient management. By synthesizing contemporary guidelines and integrating robust physiological principles, this review fosters a standardized yet flexible approach to PFT interpretation that is both scientifically sound and practically feasible. Full article

Background: Asthma and chronic obstructive pulmonary disease (COPD) are global health challenges leading to substantial morbidity and mortality. While existing guidelines emphasize evidence-based treatments, the potential therapeutic role of thermal water (TW) inhalation remains under-investigated. Methods: This systematic review followed PRISMA-P guidelines and sought to evaluate the impact of TW in asthma and COPD. A thorough literature search, performed up to May 2023, encompassed in vitro, in vivo, randomized controlled trial (RCT), non-RCT, and observational studies. Results: The review included 12 studies reporting different findings. In vitro studies suggested TW could enhance antioxidant capacity and cell proliferation. In a murine model of non-atopic asthma, TW inhalation reduced airway hyperresponsiveness and inflammation. RCTs in COPD patients indicated mixed effects, including improved quality of life, reduced airway oxidant stress, and enhanced exercise tolerance. Asthma patients exposed to water aerosols exhibited improved lung function and reduced airway inflammation. Non-RCTs showed improved lung function and antioxidant activity after TW therapy. Additionally, observational studies reported enhanced lung function and reduced airway inflammation. Conclusion: The current evidence suggests potential benefits of TW therapy in asthma and COPD. However, limited high-quality RCTs and concerns regarding occupational TW exposure necessitate further investigation. While TW therapy offers a non-invasive treatment, its therapeutic potential still needs definitive demonstration. Future research should therefore prioritize well-designed RCTs to thoroughly establish the efficacy and safety of TW as a potential therapeutic intervention for asthma and COPD. Full article

Thoracoscopic surgical biopsy has shown excellent histological characterization of undetermined interstitial lung diseases, although the morbidity rates reported are not negligible. In delicate patients, interstitial lung disease and restrictive ventilatory impairment morbidity are thought to be due at least in part to tracheal intubation with single-lung mechanical ventilation; therefore, spontaneous ventilation thoracoscopic lung biopsy (SVTLB) has been proposed as a potentially less invasive surgical option. This systematic review summarizes the results of SVTLB, focusing on diagnostic yield and operative morbidity. A systematic search for original studies regarding SVTLB published between 2010 to 2023 was performed. In addition, articles comparing SVTLB to mechanical ventilation thoracoscopic lung biopsy (MVTLB) were selected for a meta-analysis. Overall, 13 studies (two before 2017 and eleven between 2018 and 2023) entailing 675 patients were included. Diagnostic yield ranged from 84.6% to 100%. There were 64 (9.5%) complications, most of which were minor. There was no 30-day operative mortality. When comparing SVTLB to MVTLB, the former group showed a significantly lower risk of complications (p < 0.001), whereas no differences were found in diagnostic accuracy. The results of this review suggest that SVTLB is being increasingly adopted worldwide and has proven to be a safe procedure with excellent diagnostic accuracy. Full article

Asthma is a complex respiratory condition characterized by chronic airway inflammation and variable expiratory airflow limitation, affecting millions globally. Among athletes, particularly those competing at elite levels, the prevalence of respiratory conditions is notably heightened, varying between 20% and 70% across specific sports. Exercise-induced bronchoconstriction (EIB) is a common issue among athletes, impacting their performance and well-being. The prevalence rates vary based on the sport, training environment, and genetics. Exercise is a known trigger for asthma, but paradoxically, it can also improve pulmonary function and alleviate EIB severity. However, athletes’ asthma phenotypes differ, leading to varied responses to medications and challenges in management. The unique aspects in athletes include heightened airway sensitivity, allergen, pollutant exposure, and temperature variations. This review addresses EIB in athletes, focusing on pathogenesis, diagnosis, and treatment. The pathogenesis of EIB involves complex interactions between physiological and environmental factors. Airway dehydration and cooling are key mechanisms, leading to osmotic and thermal theories. Airway inflammation and hyper-responsiveness are common factors. Elite athletes often exhibit distinct inflammatory responses and heightened airway sensitivity, influenced by sport type, training, and environment. Swimming and certain sports pose higher EIB risks, with chlorine exposure in pools being a notable factor. Immune responses, lung function changes, and individual variations contribute to EIB in athletes. Diagnosing EIB in athletes requires objective testing, as baseline lung function tests can yield normal results. Both EIB with asthma (EIBA) and without asthma (EIBwA) must be considered. Exercise and indirect bronchoprovocation tests provide reliable diagnoses. In athletes, exercise tests offer effectiveness in diagnosing EIB. Spirometry and bronchodilation tests are standard approaches, but the diagnostic emphasis is shifting toward provocation tests. Despite its challenges, achieving an optimal diagnosis of EIA constitutes the cornerstone for effective management, leading to improved performance, reduced risk of complications, and enhanced quality of life. The management of EIB in athletes aligns with the general principles for symptom control, prevention, and reducing complications. Non-pharmacological approaches, including trigger avoidance and warming up, are essential. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy in athletes. Short-acting beta agonists (SABA) are discouraged as sole treatments. Leukotriene receptor antagonists (LTRA) and mast cell stabilizing agents (MCSA) are potential options. Optimal management improves the athletes’ quality of life and allows them to pursue competitive sports effectively. Full article

Chronic obstructive pulmonary disease (COPD) may coexist with type 2 diabetes mellitus (T2DM). Patients with COPD have an increased risk of developing T2DM compared with a control but, on the other side, hyperglycaemia and DM have been associated with reduced predicted levels of lung function. The mechanistic relationships between these two diseases are complicated, multifaceted, and little understood, yet they can impact treatment strategy. The potential risks and benefits for patients with T2DM treated with pulmonary drugs and the potential pulmonary risks and benefits for patients with COPD when taking antidiabetic drugs should always be considered. The interaction between the presence and/or treatment of COPD, risk of infection, presence and/or treatment of T2DM and risk of acute exacerbations of COPD (AECOPDs) can be represented as a vicious circle; however, several strategies may help to break this circle. The most effective approach to simultaneously treating T2DM and COPD is to interfere with the shared inflammatory substrate, thus targeting both lung inflammation (COPD) and vascular inflammation (DM). In any case, it is always crucial to establish glycaemic management since the reduction in lung function found in people with diabetes might decrease the threshold for clinical manifestations of COPD. In this article, we examine possible connections between COPD and T2DM as well as pharmacological strategies that could focus on these connections. Full article

Background: Pulmonary function can be impaired as a long-term consequence of SARS-CoV-2 infection. The aim of this study was to evaluate the effect of SARS-CoV-2 infection on pulmonary function, exercise tolerance, and muscle strength in healthy middle-aged military outpatients according during the period of infection. Methods: A cross-sectional study was carried out from March 2020 to November 2022 at the Military Hospital “Celio” (Rome, Italy). If someone had a diagnosis of SARS-CoV-2 infection certified by molecular nasal swab and if they performed pulmonary function tests, diffusion of carbon monoxide (DL’co), a six Minute Walk Test (6MWT), a Handgrip (HG) Test, and a One Minute Sit to Stand Test (1′STST). The included subjects were divided into two groups, A and B, according to the period of infection: A) from March 2020 to August 2021 and B) from September 2021 to October 2022. Results: One hundred fifty-three subjects were included in the study: 79 in Group A and 74 in Group B. Although the values were within the normal range, Group A had smaller FVC, FEV_1, and DL’co compared to Group B. Group A also walked a shorter distance at the 6MWT and performed fewer repetitions in the 1′STS test compared to Group B. In both groups, the DL’co (%predicted) correlated with the 6MWT distance (R² = 0.107, p < 0.001), the number of repetitions of the 1′STST (R² = 0.086, p = 0.001), and the strength at the HG test (R² = 0.08, p < 0.001). Conclusions: This study shows that the SARS-CoV-2 infection in healthy middle-aged military outpatients was more severe in the first waves than in the later ones and that, in healthy and physically fit individuals, even a marginal reduction in resting respiratory test values can have a major impact on exercise tolerance and muscles strength. Moreover, it shows that those infected more recently had symptoms related to the upper respiratory tract infection compared to those of the first waves. Full article

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP. Full article

Classically, the effects elicited by corticosteroids (CS) are mediated by the binding and activation of cytosolic glucocorticoid receptors (GR). However, several of the non-genomic effects of CS seem to be mediated by putative non-classic membrane receptors characterized by pharmacological properties that are different from those of classic cytosolic GR. Since pre-clinical findings suggest that inhaled CS (ICS) may also regulate the bronchial contractile tone via putative CS membrane-associate receptors, the aim of this review was to systematically report and discuss the impact of CS on human airway smooth muscle (ASM) contractility and airway hyperresponsiveness (AHR). Current evidence indicates that CS have significant genomic/non-genomic beneficial effects on human ASM contractility and AHR, regardless of their anti-inflammatory effects. CS are effective in reducing either the expression, synthesis or activity of α-actin, CD38, inositol phosphate, myosin light chain kinase, and ras homolog family member A in response to several pro-contractile stimuli; overall these effects are mediated by the genomic action of CS. Moreover, CS elicited a strong bronchorelaxant effect via the rapid activation of the Gsα–cyclic-adenosine-monophosphate–protein-kinase-A pathway in hyperresponsive airways. The possibility of modulating the dose of the ICS in a triple ICS/long-acting β₂-adrenoceptor agonist/long-acting muscarinic antagonist fixed-dose combination supports the use of a Triple MAintenance and Reliever Therapy (TriMART) in those asthmatic patients at Step 3–5 who may benefit from a sustained bronchodilation and have been suffering from an increased parasympathetic tone. Full article

Inhaled corticosteroids (ICS) remain the mainstay of asthma treatment, along with bronchodilators serving as control agents in combination with ICS or reliever therapy. Although current pharmacological treatments improve symptom control, health status, and the frequency and severity of exacerbations, they do not really change the natural course of asthma, including disease remission. Considering the highly heterogeneous nature of asthma, there is a strong need for innovative medications that selectively target components of the inflammatory cascade. The aim of this review was to systematically assess current investigational agents in Phase I and II randomised controlled trials (RCTs) over the last five years. Sixteen classes of novel therapeutic options were identified from 19 RCTs. Drugs belonging to different classes, such as the anti-interleukin (IL)-4Rα inhibitors, anti-IL-5 monoclonal antibodies (mAbs), anti-IL-17A mAbs, anti-thymic stromal lymphopoietin (TSLP) mAbs, epithelial sodium channel (ENaC) inhibitors, bifunctional M₃ receptor muscarinic antagonists/β₂-adrenoceptor agonists (MABAs), and anti-Fel d 1 mAbs, were found to be effective in the treatment of asthma, with lung function being the main assessed outcome across the RCTs. Several novel investigational molecules, particularly biologics, seem promising as future disease-modifying agents; nevertheless, further larger studies are required to confirm positive results from Phase I and II RCTs. Full article

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to cause long-term pulmonary sequelae. Objects: The aim of this study was to evaluate the consequences of the SARS-CoV-2 infection on pulmonary function and on the 6-min walk test related to the severity of the disease. Methods: A cross-sectional study was conducted at the “Policlinico Tor Vergata” Academic Hospital (Rome, Italy), including 75 patients evaluated in post-COVID clinics at the Respiratory Units between November 2020 and September 2021. Complete pulmonary function tests, 6-min walk tests and persistence of symptoms were performed. Results: Of the 75 subjects, 23 had mild, 16 moderate, 26 severe and 10 very severe COVID-19, classified according to WHO. Very severe patients had a lower FVC (100 ± 10%pr) compared to the other groups (116 ± 16%pr, 116 ± 13%pr, 122 ± 20%pr from mild to severe; p < 0.05) and a lower TLC (94 ± 13%pr) compared to the others (102 ± 10%pr, 108 ± 15%pr, 108 ± 12%pr from mild to severe; p < 0.05). DLco and DLco/VA were similar among groups. At the 6MWT, distance, rest and nadir SpO₂ were similar among groups, but all groups presented a significant decrease in SpO₂ from rest to nadir (Rest SpO₂: 97.0 ± 1.0% vs. Nadir SpO₂: 93.6 ± 2.7%, p < 0.01). A positive correlation was found between desaturation and delta SpO₂ (rest—nadir) (R: 0.29, p < 0.05) and the Distance Desaturation Product (R: 0.39, p < 0.01). Conclusions: These results showed that, although the PFTs are within the normal range, there is still a mild restrictive spirometric pattern after six months in very severe subjects. Moreover, the only persistent pathological sequalae of SARS-CoV-2 infection were a mild desaturation at 6MWT, despite the severity of the infection. Full article

Background: Triple fixed-dose combination (FDC) therapy is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations and/or symptoms not controlled by dual FDCs. Since no randomized controlled trials (RCTs) have directly compared the different inhaled corticosteroid/long-acting β₂-adrenoceptor agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) FDCs, we performed a meta-analysis to compare the impact of the current available ICS/LABA/LAMA FDCs in COPD. Methods: A meta-analysis was performed by connecting beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide or glycopyrrolate (BDP/FOR/GLY), budesonide (BUD)/GLY/FOR, and fluticasone furoate/umeclidinium bromide/vilanterol (FF/UMEC/VI) FDCs via ICS/LABA or LABA/LAMA FDCs arms. The safety and efficacy profiles were investigated, and the Implemented Bidimensional Surface under the cumulative ranking curve analysis (IBiS) was carried out. Protocol registration: CRD42022301189. Results: Data from 21,809 COPD patients were extracted from the ETHOS, IMPACT, KRONOS, and TRILOGY studies. No significant (p > 0.05) differences were detected across the triple FDCs with respect to the risk of exacerbation, trough forced expiratory volume in the first second (FEV₁), transition dyspnea index (TDI), St. George’s Respiratory Questionnaire (SGRQ), risk of serious adverse events (SAEs), cardiovascular (CV) SAEs, pneumonia, and all-cause mortality. According to IBiS score, BDP/FOR/GLY 200/12/25 µg twice daily (BID) was the FDC reporting the best combined efficacy/safety profile (area 41.41%), although FF/UMEC/VI 100/62.5/25 µg once daily (QD) showed the greatest efficacy profile (50.54%). The protection against mortality related to the dose of ICS. Conclusions: All triple FDCs are effective and safe in COPD regardless of the regimen of administration (twice daily vs. once daily), with no relevant difference in the risk of CV SAEs and pneumonia. Full article

Despite females being more often affected by asthma than males and the prevalence of COPD rising in females, conflicting evidence exists as to whether sex may modulate the correct inhaler technique. The aim of this study was to assess the impact of sex on the proper use of inhaler devices in asthma and COPD. A pairwise meta-analysis was performed on studies enrolling adult males and females with asthma or COPD and reporting data of patients making at least one error by inhaler device type (DPI, MDI, and SMI). The data of 6,571 patients with asthma or COPD were extracted from 12 studies. A moderate quality of evidence (GRADE +++) indicated that sex may influence the correct use of inhaler device in both asthma and COPD. The critical error rate was higher in females with asthma (OR 1.31, 95%CI 1.14–1.50) and COPD (OR 1.80, 95%CI 1.22–2.67) using DPI vs. males (p < 0.01). In addition, the use of SMI in COPD was associated with a greater rate of critical errors in females vs. males (OR 5.36, 95%CI 1.48–19.32; p < 0.05). No significant difference resulted for MDI. In conclusion, choosing the right inhaler device in agreement with sex may optimize the pharmacological treatment of asthma and COPD. Full article

COPD is an incurable disorder, characterized by a progressive alveolar tissue destruction and defective mechanisms of repair and defense leading to emphysema. Currently, treatment for COPD is exclusively symptomatic; therefore, stem cell-based therapies represent a promising therapeutic approach to regenerate damaged structures of the respiratory system and restore lung function. The aim of this study was to provide a quantitative synthesis of the efficacy profile of stem cell-based regenerative therapies and derived products in COPD patients. A systematic review and meta-analysis was performed according to PRISMA-P. Data from 371 COPD patients were extracted from 11 studies. Active treatments elicited a strong tendency towards significance in FEV₁ improvement (+71 mL 95% CI -2–145; p = 0.056) and significantly increased 6MWT (52 m 95% CI 18–87; p < 0.05) vs. baseline or control. Active treatments did not reduce the risk of hospitalization due to acute exacerbations (RR 0.77 95% CI 0.40–1.49; p > 0.05). This study suggests that stem cell-based regenerative therapies and derived products may be effective to treat COPD patients, but the current evidence comes from small clinical trials. Large and well-designed randomized controlled trials are needed to really quantify the beneficial impact of stem cell-based regenerative therapy and derived products in COPD. Full article