Showing papers in "European Respiratory Review in 2022"

Post-acute COVID-19 syndrome

Abstract: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as “post-acute COVID-19 syndrome”. Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome. Given the millions of patients infected with SARS-CoV-2 worldwide and the need for multidisciplinary management of the chronic complications, post-acute COVID-19 syndrome will be a major issue for various healthcare providers in the coming months. https://bit.ly/3lBJuXu

E-cigarettes and nicotine abstinence: a meta-analysis of randomised controlled trials

Abstract: Objectives To determine the effects of electronic cigarettes (e-cigarettes) as a therapeutic intervention compared to nicotine replacement therapy (NRT) on nicotine abstinence. Methods Two authors independently searched the PubMed, Embase, PsycInfo and Cochrane Central Register of Controlled Trials databases for articles published up to and including 10 July 2021. We included randomised controlled trials (RCTs) in which nicotine e-cigarettes were compared to NRT among current cigarette users. The primary outcome was abstaining from all nicotine-delivery devices. Secondary outcomes were 1) allocated product use (e-cigarettes or NRT) among successful cigarette quitters and 2) quitting cigarettes at the end of the trial using fixed-effect Mantel–Haenszel models. Results We included four RCTs representing 1598 adult participants (51.0% females). The mean age of participants in these studies ranged from 41 to 54 years, while average baseline smoking ranged from 14 to 21 cigarettes per day. Compared to NRT, e-cigarette use was associated with lower nicotine abstinence rates at the longest follow-up (risk ratio 0.50 (95% CI 0.32–0.77)). Among successful cigarette quitters, the risk of allocated product use by the end of the observational time was higher for e-cigarette users compared to NRT (risk ratio 8.94 (95% CI 3.98–20.07)). E-cigarette users had higher cigarette smoking cessation rates compared to NRT users (risk ratio 1.58 (95% CI 1.20–2.08)). Conclusions The use of e-cigarettes as a therapeutic intervention for smoking cessation may lead to permanent nicotine dependence. Clinicians should not recommend e-cigarettes for smoking cessation due to the risk of permanent nicotine dependence https://bit.ly/358oToy

Clinical significance and applications of oscillometry

Abstract: Recently, “Technical standards for respiratory oscillometry” was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease. This paper provides a current review of the interpretation, clinical significance and application of oscillometry in respiratory medicine, with special emphasis on limitations of evidence and suggestions for future research. https://bit.ly/3GQPViA

Role of air pollutants in airway epithelial barrier dysfunction in asthma and COPD

Abstract: Chronic exposure to environmental pollutants is a major contributor to the development and progression of obstructive airway diseases, including asthma and COPD. Understanding the mechanisms underlying the development of obstructive lung diseases upon exposure to inhaled pollutants will lead to novel insights into the pathogenesis, prevention and treatment of these diseases. The respiratory epithelial lining forms a robust physicochemical barrier protecting the body from inhaled toxic particles and pathogens. Inhalation of airborne particles and gases may impair airway epithelial barrier function and subsequently lead to exaggerated inflammatory responses and airway remodelling, which are key features of asthma and COPD. In addition, air pollutant-induced airway epithelial barrier dysfunction may increase susceptibility to respiratory infections, thereby increasing the risk of exacerbations and thus triggering further inflammation. In this review, we discuss the molecular and immunological mechanisms involved in physical barrier disruption induced by major airborne pollutants and outline their implications in the pathogenesis of asthma and COPD. We further discuss the link between these pollutants and changes in the lung microbiome as a potential factor for aggravating airway diseases. Understanding these mechanisms may lead to identification of novel targets for therapeutic intervention to restore airway epithelial integrity in asthma and COPD. Exposure to air pollution induces airway epithelial barrier dysfunction through several mechanisms including increased oxidative stress, exaggerated cytokine responses and impaired host defence, which contributes to development of asthma and COPD. https://bit.ly/3DHL1CA

Bidirectional relationships of comorbidity with obstructive sleep apnoea

Abstract: Obstructive sleep apnoea (OSA) is frequently associated with comorbidities that include metabolic, cardiovascular, renal, pulmonary and neuropsychiatric. There is considerable evidence that OSA is an independent risk factor for many of these comorbidities but, more recently, there is evidence that some of these comorbidities may predispose to the development of OSA. Thus, there is growing evidence of a bidirectional relationship between OSA and comorbidity, especially for heart failure, metabolic syndrome and stroke. Potential mechanisms of bidirectional relationships differ in individual comorbidities with fluid retention and redistribution being especially important in heart failure and end-stage renal disease, whereas neural mechanisms may be more important in diabetes mellitus and stroke. The evidence for other comorbidities, such as hypertension and atrial fibrillation, support these being more a consequence of OSA with limited evidence to support a bidirectional relationship. The present review explores the evidence for such bidirectional relationships with a particular perspective on comorbidities that may predispose to OSA. The impact of therapy in bidirectional relationships is also reviewed, which highlights the clinical importance of accurate diagnosis. This aspect is especially true of COPD, where the identification of co-existing OSA has important implications for optimum therapy. Obstructive sleep apnoea (OSA) is an independent risk factor for comorbidity, especially cardiometabolic. However, some comorbidities may be risk factors for OSA, supporting a bidirectional relationship that may have important implications for treatment. https://bit.ly/3BbJy6V

COVID-19 and tuberculosis: the double whammy of respiratory pathogens

Abstract: Prior to coronavirus disease 2019 (COVID-19), tuberculosis (TB) was the worst killer among infectious diseases. The union of these two obnoxious respiratory diseases can be devastating, with severe public health implications. The COVID-19 pandemic has affected all TB-elimination programmes due to the severe burden on healthcare systems and the diversion of funds and attention towards controlling the pandemic. The emerging data show that the COVID-19 pandemic caused a marked decrease in case notifications and bacille Calmette–Guérin immunisations, ultimately promoting disease transmission and increasing the susceptible population. The similarity between the clinical characteristics of TB and COVID-19 adds to the public health complications, with evidence of immune dysregulation in both cases leading to severe consequences. Clinical evidence suggests that severe acute respiratory syndrome coronavirus 2 infection predisposes patients to TB infection or may lead to reactivation of latent disease. Similarly, underlying TB disease can worsen COVID-19. Treatment options are limited in COVID-19; therefore, using immunosuppressive and immunomodulatory regimens that can modulate the concomitant bacterial infection and interaction with anti-TB drugs requires caution. Thus, considering the synergistic impact of these two respiratory diseases, it is crucial to manage both diseases to combat the syndemic of TB and COVID-19. M. tuberculosis is a deadly human pathogen, and the emergence of COVID-19 has hampered TB control measures. Better co-infection management can prevent disease-related complications and produce favourable outcomes. https://bit.ly/3LiiV57

The evolving landscape of sex-based differences in lung cancer: a distinct disease in women

Abstract: In stark contrast to a few decades ago when lung cancer was predominantly a disease of men who smoke, incidence rates of lung cancer in women are now comparable to or higher than those in men and are rising alarmingly in many parts of the world. Women face a unique set of risk factors for lung cancer compared to men. These include exogenous exposures including radon, prior radiation, and fumes from indoor cooking materials such as coal, in addition to endogenous exposures such as oestrogen and distinct genetic polymorphisms. Current screening guidelines only address tobacco use and likely underrepresent lung cancer risk in women. Women were also not well represented in some of the landmark prospective studies that led to the development of current screening guidelines. Women diagnosed with lung cancer have a clear mortality benefit compared to men even when other clinical and demographic characteristics are accounted for. However, there may be sex-based differences in outcomes and side effects of systemic therapy, particularly with chemotherapy and immunotherapy. Ongoing research is needed to better investigate these differences to address the rapidly changing demographics of lung cancer worldwide. Sex-based differences in lung cancer span the care continuum. This suggests lung cancer may increasingly be viewed as a distinct disease in women, with implications for screening and treatment. Lung cancer research should capture these sex-based differences. https://bit.ly/2WfhaB4

Diagnosis, course and management of hypersensitivity pneumonitis

Abstract: Hypersensitivity pneumonitis (HP) is a complex and heterogeneous interstitial lung disease (ILD) that occurs when susceptible individuals develop an exaggerated immune response to an inhaled antigen. In this review, we discuss the latest guidelines for the diagnostic evaluation of patients with suspected HP, the importance of identifying patients with fibrotic and progressive disease, and the evidence supporting the drugs commonly used in the treatment of HP. Differential diagnosis of HP can be challenging and requires a thorough exposure history, multidisciplinary discussion of clinical and radiologic data, and, in some cases, assessment of bronchoalveolar lavage lymphocytosis and histopathologic findings. Patients with HP may be categorised as having non-fibrotic or fibrotic HP. The presence of fibrosis is associated with worse outcomes. A proportion of patients with fibrotic HP develop a progressive phenotype, characterised by worsening fibrosis, decline in lung function and early mortality. There are no established guidelines for the treatment of HP. Antigen avoidance should be implemented wherever possible. Immunosuppressants are commonly used in patients with HP but have not been shown to slow the worsening of fibrotic disease. Nintedanib, a tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for slowing the progression of chronic fibrosing ILDs with a progressive phenotype, including progressive fibrotic HP. Non-pharmacological interventions, such as oxygen therapy, pulmonary rehabilitation and supportive care, may be important components of the overall care of patients with progressive HP. Guideline statements for the diagnosis of hypersensitivity pneumonitis have recently been published by the ATS/JRS/ALAT and CHEST. This review examines differences in the two guideline statements and discusses current management options. https://bit.ly/3o6uJh2

Prognostic factors for mortality, intensive care unit and hospital admission due to SARS-CoV-2: a systematic review and meta-analysis of cohort studies in Europe

Abstract: Background As mortality from coronavirus disease 2019 (COVID-19) is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age-/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations. Methods We performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including death, hospitalisation, intensive care unit (ICU) admission and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11 June 2021 in Ovid Medline and Embase. Results are presented as odds ratios with 95% confidence intervals and absolute risk differences in deaths per 1000 COVID-19 patients. Findings We included 88 cohort studies with age-/gender-adjusted data from 6 653 207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke and liver disease. Interpretation The results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of nonpharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions. There is a strong association between specific prognostic factors and mortality and hospital admission due to SARS-CoV-2, including, but not limited to, diabetes, cardiovascular diseases and respiratory diseases. https://bit.ly/3Qo4zCc

Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy

Abstract: Neutrophilic inflammation has a key role in the pathophysiology of multiple chronic lung diseases. The formation of neutrophil extracellular traps (NETs) has emerged as a key mechanism of disease in neutrophilic lung diseases including asthma, COPD, cystic fibrosis and, most recently, bronchiectasis. NETs are large, web-like structures composed of DNA and anti-microbial proteins that are able to bind pathogens, prevent microbial dissemination and degrade bacterial virulence factors. The release of excess concentrations of proteases, antimicrobial proteins, DNA and histones, however, also leads to tissue damage, impaired mucociliary clearance, impaired bacterial killing and increased inflammation. A number of studies have linked airway NET formation with greater disease severity, increased exacerbations and overall worse disease outcomes across the spectrum of airway diseases. Treating neutrophilic inflammation has been challenging in chronic lung disease because of the delicate balance between reducing inflammation and increasing the risk of infections through immunosuppression. Novel approaches to suppressing NET formation or the associated inflammation are in development and represent an important therapeutic target. This review will discuss the relationship between NETs and the pathophysiology of cystic fibrosis, asthma, COPD and bronchiectasis, and explore the current and future development of NET-targeting therapies. NETs contribute to the pathophysiology of chronic lung disease. Immunomodulating therapies that may reduce inflammatory mediators and NET formation, without compromising bacterial clearance, offer a new treatment path for patients. https://bit.ly/3fyJC6I

Sex, gender and the pulmonary physiology of exercise

Abstract: In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise. Biological sex can influence the pulmonary response to exercise in healthy individuals across the lifespan https://bit.ly/3ejMDrv

Just breathe: a review of sex and gender in chronic lung disease

Abstract: Chronic lung diseases are the third leading cause of death worldwide and are increasing in prevalence over time. Although much of our traditional understanding of health and disease is derived from study of the male of the species – be it animal or human – there is increasing evidence that sex and gender contribute to differences in disease risk, prevalence, presentation, severity, treatment approach, response and outcomes. Chronic obstructive pulmonary disease, asthma and bronchiectasis represent the most prevalent and studied chronic lung diseases and have key sex- and gender-based differences which are critical to consider and incorporate into clinical and research approaches. Mechanistic differences present opportunities for therapeutic development whereas behavioural and clinical differences on the part of patients and providers present opportunities for greater education and understanding at multiple levels. In this review, we seek to summarise the sex- and gender-based differences in key chronic lung diseases and outline the clinical and research implications for stakeholders. Sex and gender differences impact lung diseases throughout the lifespan and are critical to consider and incorporate into research and clinical care to optimise outcomes. https://bit.ly/38hAhfY

Eosinophils and eosinophilic immune dysfunction in health and disease

Abstract: The functions ascribed to eosinophils have classically been limited to host defence against certain parasitic infections and potentially deleterious effects in the setting of specific diseases that are associated with elevated eosinophil counts in blood and/or tissue. The ability to induce eosinophil depletion either experimentally in animal models or through targeted therapies in humans has extended our understanding of the roles played by eosinophils in health and homeostasis as well as in disease pathogenesis. When associated with human disease aetiology, the eosinophil takes on a pathogenic rather than a protective role. This maladaptive response, called “eosinophilic immune dysfunction” herein, appears central to exacerbation pathogenesis and disease control in severe asthma and may be involved in the aetiology of other eosinophil-related conditions ranging from organ-system-limited diseases such as phenotypic subsets of chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyposis to more broadly systemic diseases such as eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. In this review, we describe the evidence supporting eosinophilic functions related to health and homeostasis and explore the contribution of eosinophilic immune dysfunction to human disease. The current era of therapies that specifically target eosinophils has yielded new insights into the functional significance of eosinophils in the maintenance of health and the effects of eosinophilic immune dysfunction on disease pathogenesis. https://bit.ly/3pVPLR5

Predicting the pulmonary effects of long-term e-cigarette use: are the clouds clearing?

Abstract: Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever-growing complexity. Given their increasing use by ex-smokers, smokers and never-smokers, it is important to evaluate evidence of their potential pulmonary effects and predict effects of long-term use, since there has been insufficient time to study a chronic user cohort. It is crucial to evaluate indicators of harm seen in cigarette use, and those potentially unique to e-cigarette exposure. Evaluation must also account for the vast variation in e-cigarette devices (now including at least five generations of devices) and exposure methods used in vivo and in vitro. Thus far, short-term use cohort studies, combined with in vivo and in vitro models, have been used to probe for the effects of e-cigarette exposure. The effects and mechanisms identified, including dysregulated inflammation and decreased pathogen resistance, show concerning overlaps with the established effects of cigarette smoke exposure. Additionally, research has identified a signature of dysregulated lipid processing, which is unique to e-cigarette exposure. This review will evaluate the evidence of pulmonary effects of, and driving mechanisms behind, e-cigarette exposure, which have been highlighted in emerging literature, and highlight the gaps in current knowledge. Such a summary allows understanding of the ongoing debate into e-cigarette regulation, as well as prediction and potential mitigation of future problems surrounding e-cigarette use. Long-term e-cigarette exposure may result in pulmonary inflammation and reduced resistance to respiratory infections, which partially reflects the established effects of cigarette exposure, due to a combination of nicotine exposure and oxidative stress. https://bit.ly/3zwMFE5

Chronic lung diseases: entangled in extracellular matrix

Abstract: The extracellular matrix (ECM) is the scaffold that provides structure and support to all organs, including the lung; however, it is also much more than this. The ECM provides biochemical and biomechanical cues to cells that reside or transit through this micro-environment, instructing their responses. The ECM structure and composition changes in chronic lung diseases; how such changes impact disease pathogenesis is not as well understood. Cells bind to the ECM through surface receptors, of which the integrin family is one of the most widely recognised. The signals that cells receive from the ECM regulate their attachment, proliferation, differentiation, inflammatory secretory profile and survival. There is extensive evidence documenting changes in the composition and amount of ECM in diseased lung tissues. However, changes in the topographical arrangement, organisation of the structural fibres and stiffness (or viscoelasticity) of the matrix in which cells are embedded have an undervalued but strong impact on cell phenotype. The ECM in diseased lungs also changes in physical and biomechanical ways that drive cellular responses. The characteristics of these environments alter cell behaviour and potentially orchestrate perpetuation of lung diseases. Future therapies should target ECM remodelling as much as the underlying culprit cells. Important biochemical and biomechanical cues from the extracellular matrix are disrupted in chronic lung diseases, altering the fate of resident lung cells and trafficking immune cells, and thereby contributing to disease development and progression https://bit.ly/3FgiQvc

State-of-the-art review of lung imaging in cystic fibrosis with recommendations for pulmonologists and radiologists from the “iMAging managEment of cySTic fibROsis” (MAESTRO) consortium

Abstract: Objective Imaging represents an important noninvasive means to assess cystic fibrosis (CF) lung disease, which remains the main cause of morbidity and mortality in CF patients. While the development of new imaging techniques has revolutionised clinical practice, advances have posed diagnostic and monitoring challenges. The authors aim to summarise these challenges and make evidence-based recommendations regarding imaging assessment for both clinicians and radiologists. Study design A committee of 21 experts in CF from the 10 largest specialist centres in Italy was convened, including a radiologist and a pulmonologist from each centre, with the overall aim of developing clear and actionable recommendations for lung imaging in CF. An a priori threshold of at least 80% of the votes was required for acceptance of each statement of recommendation. Results After a systematic review of the relevant literature, the committee convened to evaluate 167 articles. Following five RAND conferences, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 28 main statements. Conclusions There is a need for international guidelines regarding the appropriate timing and selection of imaging modality for patients with CF lung disease; timing and selection depends upon the clinical scenario, the patient's age, lung function and type of treatment. Despite its ubiquity, the use of the chest radiograph remains controversial. Both computed tomography and magnetic resonance imaging should be routinely used to monitor CF lung disease. Future studies should focus on imaging protocol harmonisation both for computed tomography and for magnetic resonance imaging. The introduction of artificial intelligence imaging analysis may further revolutionise clinical practice by providing fast and reliable quantitative outcomes to assess disease status. To date, there is no evidence supporting the use of lung ultrasound to monitor CF lung disease. There is a need for international guidelines regarding the appropriate timing and selection of imaging modality for patients with cystic fibrosis lung disease. https://bit.ly/3HwjUvG

WASOG statement on the diagnosis and management of sarcoidosis-associated pulmonary hypertension

Abstract: Sarcoidosis-associated pulmonary hypertension (SAPH) is an important complication of advanced sarcoidosis. Over the past few years, there have been several studies dealing with screening, diagnosis and treatment of SAPH. This includes the results of two large SAPH-specific registries. A task force was established by the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) to summarise the current level of knowledge in the area and provide guidance for the management of patients. A group of sarcoidosis and pulmonary hypertension experts participated in this task force. The committee developed a consensus regarding initial screening including who should undergo more specific testing with echocardiogram. Based on the results, the committee agreed upon who should undergo right-heart catheterisation and how to interpret the results. The committee felt there was no specific phenotype of a SAPH patient in whom pulmonary hypertension-specific therapy could be definitively recommended. They recommended that treatment decisions be made jointly with a sarcoidosis and pulmonary hypertension expert. The committee recognised that there were significant defects in the current knowledge regarding SAPH, but felt the statement would be useful in directing future studies. Sarcoidosis-associated pulmonary hypertension is a significant cause of morbidity and mortality. A guide to screening, diagnosis and treatment has been developed by a team of experts. https://bit.ly/3FzOcgb

Understanding the pathogenesis of occupational coal and silica dust-associated lung disease

Abstract: Workers in the mining and construction industries are at increased risk of respiratory and other diseases as a result of being exposed to harmful levels of airborne particulate matter (PM) for extended periods of time. While clear links have been established between PM exposure and the development of occupational lung disease, the mechanisms are still poorly understood. A greater understanding of how exposures to different levels and types of PM encountered in mining and construction workplaces affect pathophysiological processes in the airways and lungs and result in different forms of occupational lung disease is urgently required. Such information is needed to inform safe exposure limits and monitoring guidelines for different types of PM and development of biomarkers for earlier disease diagnosis. Suspended particles with a 50% cut-off aerodynamic diameter of 10 µm and 2.5 µm are considered biologically active owing to their ability to bypass the upper respiratory tract's defences and penetrate deep into the lung parenchyma, where they induce potentially irreversible damage, impair lung function and reduce the quality of life. Here we review the current understanding of occupational respiratory diseases, including coal worker pneumoconiosis and silicosis, and how PM exposure may affect pathophysiological responses in the airways and lungs. We also highlight the use of experimental models for better understanding these mechanisms of pathogenesis. We outline the urgency for revised dust control strategies, and the need for evidence-based identification of safe level exposures using clinical and experimental studies to better protect workers’ health. The re-emergence of CWP highlights a lack of knowledge of and/or effective safe level exposure limits for occupational exposure to dust. This review identifies and highlights potential factors and discusses parthenogenesis of silicosis and CWP in detail. https://bit.ly/3Mwv6uN

Current unmet needs and potential solutions to uncontrolled asthma

Abstract: Despite the availability of effective inhaled therapies, many patients with asthma have poor asthma control. Uncontrolled asthma presents a significant burden on the patient and society, and, for many, remains largely preventable. There are numerous reasons why a patient may remain uncontrolled despite access to therapies, including incorrect inhaler technique, poor adherence to treatment, oversight of triggers and suboptimal medical care. Shared decision-making, good patient–clinician communication, supported self-management, multidisciplinary patient education, new technology and risk stratification may all provide solutions to this major unmet need in asthma. Novel treatments such as biologics could benefit patients’ lives, while the investigations into biomarkers, non-Type 2 asthma, treatable traits and disease modification give an exciting glimpse into the future of asthma care. Despite effective therapies, many patients with asthma have poor asthma control, which is preventable. The benefits of shared decision-making, supported self-management, risk stratification and novel treatments in transforming patient care are reviewed. https://bit.ly/3A386Nm

Extracellular vesicle-mediated cellular crosstalk in lung repair, remodelling and regeneration

Abstract: The unperturbed lung is highly quiescent, with a remarkably low level of cell turnover. However, once damaged, the lung shows an extensive regenerative capacity, with resident progenitor cell populations re-entering the cell cycle and differentiating to promote repair. This quick and dramatic repair response requires interactions among more than 40 different cell lineages in the lung, and defects in any of these processes can lead to various lung pathologies. Understanding the mechanisms of interaction in lung injury, repair and regeneration thus has considerable practical and therapeutic implications. Moreover, therapeutic strategies for replacing lung progenitor cells and their progeny through cell therapy have gained increasing attention. In the last decade, extracellular vesicles (EVs), including exosomes, have been recognised as paracrine mediators through the transfer of biological cargo. Recent work has revealed that EVs are involved in lung homeostasis and diseases. In addition, EVs derived from specific cells or tissues have proven to be a promising cell-free modality for the treatment of lung diseases. This review highlights the EV-mediated cellular crosstalk that regulates lung homeostasis and discusses the potential of EV therapeutics for lung regenerative medicine. Extracellular vesicles are important intracellular mediators in lung repair, remodelling and regeneration, and are potential therapeutic agents for lung regenerative medicine https://bit.ly/3jhc7sb

Burden of respiratory syncytial virus infection in older and high-risk adults: a systematic review and meta-analysis of the evidence from developed countries

Abstract: Background Respiratory syncytial virus (RSV) significantly impacts the health of older and high-risk adults (those with comorbidities). We aimed to synthesise the evidence on RSV disease burden and RSV-related healthcare utilisation in both populations. Methods We searched Embase and MEDLINE for papers published between 2000 and 2019 reporting the burden and clinical presentation of symptomatic RSV infection and the associated healthcare utilisation in developed countries in adults aged ≥60 years or at high risk. We calculated pooled estimates using random-effects inverse variance-weighted meta-analysis. Results 103 out of 3429 articles met the inclusion criteria. Among older adults, RSV caused 4.66% (95% CI 3.34–6.48%) of symptomatic respiratory infections in annual studies and 7.80% (95% CI 5.77–10.45%) in seasonal studies; RSV-related case fatality proportion (CFP) was 8.18% (95% CI 5.54–11.94%). Among high-risk adults, RSV caused 7.03% (95% CI 5.18–9.48%) of symptomatic respiratory infections in annual studies, and 7.69% (95% CI 6.23–9.46%) in seasonal studies; CFP was 9.88% (95% CI 6.66–14.43%). Data paucity impaired the calculation of estimates on population incidence, clinical presentation, severe outcomes and healthcare-related utilisation. Conclusions Older and high-risk adults frequently experience symptomatic RSV infection, with appreciable mortality; however, detailed data are lacking. Increased surveillance and research are needed to quantify population-based disease burden and facilitate RSV treatments and vaccine development. In developed countries, older adults and those at risk of complications frequently experience symptomatic respiratory syncytial virus infection. However, more data on key health indicators are required to clarify disease burden and impact in these groups. https://bit.ly/3zvEHxc

Cardiac consequences of intermittent hypoxia: a matter of dose? A systematic review and meta-analysis in rodents

Abstract: Aim Intermittent hypoxia (IH) is considered to be a major contributor to obstructive sleep apnoea-related cardiovascular consequences. The present meta-analysis aimed to assess the effects of IH on cardiac remodelling, function and infarct size after myocardial ischaemia across different rodent species and IH severities. Methods and results Relevant articles from PubMed, Embase and Web of Science were screened. We performed a random effect meta-analysis to assess the effect of IH on myocardium in rodents by using standardised mean difference (SMD). Studies using rodents exposed to IH and outcomes related to cardiac remodelling, contractile function and response to myocardial ischaemia–reperfusion were included. 5217 articles were screened and 92 were included, demonstrating that IH exposure induced cardiac remodelling, characterised by cardiomyocyte hypertrophy (cross-sectional area: SMD=2.90, CI (0.82–4.98), I2=94.2%), left ventricular (LV) dilation (LV diameter: SMD=0.64, CI (0.18–1.10), I2=88.04%), interstitial fibrosis (SMD=5.37, CI (3.22–7.53), I2=94.8) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling: SMD=6.70, CI (2.96–10.44), I2=95.9). These structural changes were accompanied by a decrease in LV ejection fraction (SMD=−1.82, CI (−2.52–−1.12), I2=94.22%). Importantly, most of the utilised IH protocols mimicked extremely severe hypoxic disease. Concerning infarct size, meta-regression analyses highlighted an ambivalent role of IH, depending on its severity. Indeed, IH exposure with inspiratory oxygen fraction (FIO2) <7% was associated with an increase in infarct size, whereas a reduced infarct size was reported for FIO2 levels above 10%. Heterogeneity between studies, small study effect and poor reporting of methods in included articles limited the robustness of the meta-analysis findings. Conclusion This meta-analysis demonstrated that severe IH systematically induces cardiac remodelling and contractile dysfunction in rodents, which might trigger or aggravate chronic heart failure. Interestingly, this meta-analysis showed that, depending on stimulus severity, IH exhibits both protective and aggravating effects on infarct size after experimental ischaemia–reperfusion procedures. This meta-analysis shows that IH induces cardiac remodelling and contractile dysfunction in rodents, independently of IH characteristics. Conversely, the dual response to myocardial ischaemia–reperfusion seems to be related to IH intensity and duration. https://bit.ly/3rdnR32

Holy Grail: the journey towards disease modification in asthma

Abstract: At present, there is no cure for asthma, and treatment typically involves therapies that prevent or reduce asthma symptoms, without modifying the underlying disease. A “disease-modifying” treatment can be classed as able to address the pathogenesis of a disease, preventing progression or leading to a long-term reduction in symptoms. Such therapies have been investigated and approved in other indications, e.g. rheumatoid arthritis and immunoglobulin E-mediated allergic disease. Asthma's heterogeneous nature has made the discovery of similar therapies in asthma more difficult, although novel therapies (e.g. biologics) may have the potential to exhibit disease-modifying properties. To investigate the disease-modifying potential of a treatment, study design considerations can be made, including: appropriate end-point selection, length of trial, age of study population (key differences between adults/children in physiology, pathology and drug metabolism) and comorbidities in the patient population. Potential future focus areas for disease-modifying treatments in asthma include early assessments (e.g. to detect patterns of remodelling) and interventions for patients genetically susceptible to asthma, interventions to prevent virally induced asthma and therapies to promote a healthy microbiome. This review explores the pathophysiology of asthma, the disease-modifying potential of current asthma therapies and the direction future research may take to achieve full disease remission or prevention. Asthma is a complex, heterogeneous disease, which currently has no cure; this review explores the disease-modifying potential of asthma therapies and the direction future research may take to achieve disease remission or prevention. https://bit.ly/31AxYou

Effectiveness of home-based pulmonary rehabilitation: systematic review and meta-analysis

Abstract: Introduction Despite proven effectiveness for people with chronic respiratory diseases, practical barriers to attending centre-based pulmonary rehabilitation (centre-PR) limit accessibility. We aimed to review the clinical effectiveness, components and completion rates of home-based pulmonary rehabilitation (home-PR) compared to centre-PR or usual care. Methods and analysis Using Cochrane methodology, we searched (January 1990 to August 2021) six electronic databases using a PICOS (population, intervention, comparison, outcome, study type) search strategy, assessed Cochrane risk of bias, performed meta-analysis and narrative synthesis to answer our objectives and used the Grading of Recommendations, Assessment, Development and Evaluations framework to rate certainty of evidence. Results We identified 16 studies (1800 COPD patients; 11 countries). The effects of home-PR on exercise capacity and/or health-related quality of life (HRQoL) were compared to either centre-PR (n=7) or usual care (n=8); one study used both comparators. Compared to usual care, home-PR significantly improved exercise capacity (standardised mean difference (SMD) 0.88, 95% CI 0.32–1.44; p=0.002) and HRQoL (SMD −0.62, 95% CI −0.88–−0.36; p<0.001). Compared to centre-PR, home-PR showed no significant difference in exercise capacity (SMD −0.10, 95% CI −0.25–0.05; p=0.21) or HRQoL (SMD 0.01, 95% CI −0.15–0.17; p=0.87). Conclusion Home-PR is as effective as centre-PR in improving functional exercise capacity and quality of life compared to usual care, and is an option to enable access to pulmonary rehabilitation. Home-based pulmonary rehabilitation is as effective as centre-based in improving exercise capacity and quality of life, and is an option for people with COPD whose access to pulmonary rehabilitation centres is difficult. https://bit.ly/39HkMm4

The threat of multidrug-resistant/extensively drug-resistant Gram-negative respiratory infections: another pandemic

Abstract: Antibiotic resistance is recognised as a global threat to human health by national healthcare agencies, governments and medical societies, as well as the World Health Organization. Increasing resistance to available antimicrobial agents is of concern for bacterial, fungal, viral and parasitic pathogens. One of the greatest concerns is the continuing escalation of antimicrobial resistance among Gram-negative bacteria resulting in the endemic presence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) pathogens. This concern is heightened by the identification of such MDR/XDR Gram-negative bacteria in water and food sources, as colonisers of the intestine and other locations in both hospitalised patients and individuals in the community, and as agents of all types of infections. Pneumonia and other types of respiratory infections are among the most common infections caused by MDR/XDR Gram-negative bacteria and are associated with high rates of mortality. Future concerns are already heightened due to emergence of resistance to all existing antimicrobial agents developed in the past decade to treat MDR/XDR Gram-negative bacteria and a scarcity of novel agents in the developmental pipeline. This clinical scenario increases the likelihood of a future pandemic caused by MDR/XDR Gram-negative bacteria. Antimicrobial resistance continues to rise among Gram-negative bacteria, leading to greater morbidity, mortality, lengths of stay and costs. The level of resistance is approaching pandemic proportions, requiring an urgent call to address this problem. https://bit.ly/3NTnDqK

Prevalence, risk factors and treatments for post-COVID-19 breathlessness: a systematic review and meta-analysis

Abstract: Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23–29) when measuring the presence/absence of the symptom, and 41% (95% CI 34–48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1–6 months to 7–12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness. A sizable proportion of patients with COVID-19 experienced post-COVID breathlessness, and the prevalence estimate varied by population characteristics and methodological approaches. Further research on mechanisms and interventions for this sequela is needed. https://bit.ly/3P5ayv6

Incidental discovery of interstitial lung disease: diagnostic approach, surveillance and perspectives

Abstract: The incidental discovery of pre-clinical interstitial lung disease (ILD) has led to the designation of interstitial lung abnormalities (ILA), a radiological entity defined as the incidental finding of computed tomography (CT) abnormalities affecting more than 5% of any lung zone. Two recent documents have redefined the borders of this entity and made the recommendation to monitor patients with ILA at risk of progression. In this narrative review, we will focus on some of the limits of the current approach, underlying the potential for progression to full-blown ILD of some patients with ILA and the numerous links between subpleural fibrotic ILA and idiopathic pulmonary fibrosis (IPF). Considering the large prevalence of ILA in the general population (7%), restricting monitoring only to cases considered at risk of progression appears a reasonable approach. However, this suggestion should not prevent pulmonary physicians from pursuing an early diagnosis of ILD and timely treatment where appropriate. In cases of suspected ILD, whether found incidentally or not, the pulmonary physician is still required to make a correct ILD diagnosis according to current guidelines, and eventually treat the patient accordingly. In patients with interstitial lung abnormalities (ILA), monitoring of those at risk of progression is currently recommended, and pulmonary physicians should pursue an early diagnosis when ILA become clinically significant to facilitate timely treatment https://bit.ly/3HKOQc8

Management of Mycobacterium avium complex and Mycobacterium abscessus pulmonary disease: therapeutic advances and emerging treatments

Abstract: Nontuberculous mycobacterial pulmonary disease (NTM-PD) remains a challenging condition to diagnose and treat effectively. Treatment of NTM-PD is prolonged, frequently associated with adverse effects and has variable success. In this review, we consider the factors influencing clinicians when treating NTM-PD and discuss outcomes from key studies on the pharmacological management of Mycobacterium avium complex pulmonary disease and M. abscessus pulmonary disease. We highlight issues relating to treatment-related toxicity and provide an overview of repurposed and emerging therapies for NTM-PD. Despite advances in treatment regimens for nontuberculous mycobacterial pulmonary disease, significant challenges remain. Repurposed and emerging therapies may hold promise. https://bit.ly/3IBPh9q

Diagnostic yield and safety of transbronchial lung cryobiopsy and surgical lung biopsy in interstitial lung diseases: a systematic review and meta-analysis

Abstract: Introduction: Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic pattern in interstitial lung disease (ILD). Methods: A systematic literature search of the PubMed and Embase databases, from October 2010 to October 2020, was conducted to identify studies that reported on diagnostic yield or safety of VATS or TBLC in the diagnosis of ILD. Results: 43 studies were included. 23 evaluated the diagnostic yield of TBLC after multidisciplinary discussion, with a pooled diagnostic yield of 76.8% (95% confidence interval (CI) 70.6–82.1), rising to 80.7% in centres that performed ≥70 TBLC. 10 studies assessed the use of VATS and the pooled diagnostic yield was 93.5% (95% CI 88.3–96.5). In TBLC, pooled incidences of complications were 9.9% (95% CI 6.8–14.3) for significant bleeding (6.9% for centres with ≥70 TBLC), 5.6% (95% CI 3.8–8.2) for pneumothorax treated with a chest tube and 1.4% (95% CI 0.9–2.2) for acute exacerbation of ILD after TBLC. The mortality rates were 0.6% and 1.7% for TBLC and VATS, respectively. Conclusions: TBLC has a fairly good diagnostic yield, an acceptable safety profile and a lower mortality rate than VATS. The best results are obtained from more experienced centres. Transbronchial lung cryobiopsy has a reasonable diagnostic yield of over 80% in experienced centres, with a better safety profile and lower mortality rate than video-assisted thoracoscopic surgery biopsy in interstitial lung diseases. https://bit.ly/3Nqozmn

Assessing adherence to inhaled therapies in asthma and the emergence of electronic monitoring devices

Abstract: Infrequent use of inhaled corticosteroids (ICS) and/or over-reliance of short-acting β-agonists (SABA) are recognised as key contributors to increased morbidity and mortality in asthma. The most frequent measures of ICS adherence and SABA use rely on patient-reported questionnaires or prescription refill records, neither of which are considered sufficiently reliable. Technological advancements in the development of electronic monitoring of inhaler devices allow for monitoring of use, as well as recording of and feedback on inhaler technique for some devices. Most electronic monitoring devices (EMDs) are paired with a smartphone application, allowing patients to set reminders and display both preventer and reliever use over time. This allows identification of intentional and unintentional ICS non-adherence as well as frequency of SABA use. This information assists clinicians in distinguishing difficult-to-control from severe asthma. Although additional evidence is required to assess the impact of EMDs on clinical outcome measures such as exacerbation rate, the introduction of EMDs into the asthma armoury is a significant step forward in asthma care with the potential to improve asthma-related outcomes. Technological advancements in the development of electronic monitoring devices allow for identification of intentional and unintentional ICS non-adherence in asthma. https://bit.ly/37MPYip