Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. METHODS: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. RESULTS: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (ß=0.02 L, 95% CI -0.02-0.06 L) or lower FEV1/FVC (ß=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income. CONCLUSION: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.

Tularaemia: a case report and review.

Tularaemia is a rare infectious disease caused by Francisella tularensis. In Poland, F. tularensis infections are caused by F. tularensis subspecies holarctica (type B). The disease is widespread among multiple animal species. Humans are usually infected via insect bites and less commonly by other routes (contact with animals, inhalation of contaminated aerosol or dust, or oral route). In recent years, the prevalence of tularaemia in Poland was slightly more than dozen cases per year. Depending on the route of infection, the disease has various clinical presentations, of which the most common is the ulceroglandular form. We present a typical case of this clinical form, along with information on epidemiology, clinical presentation, diagnosis, and treatment of this rare disease. Because of a low prevalence and miscellaneous clinical features, the diagnosis is often delayed. Tularaemia should be included in the differential diagnosis of fever with local lymph node enlargement as well as atypical cases of upper airway infections and pneumonia.

Chronic airflow obstruction and ambient particulate air pollution.

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.

Quality and methodology of clinical practice guidelines on antiviral pharmacotherapy for COVID­19 during the early phase of the pandemic.

INTRODUCTION: Despite availability of reliable guidelines development methods, the risk of producing less reliable documents may be higher when the guidelines are developed rapidly. OBJECTIVES: The aim of this study was to assess quality of guidelines on coronavirus disease 2019 (COVID-19), developed in the early stages of COVID-19 pandemic and assess if recommendations for pharmacotherapy were supported by evidence. METHODS: We performed the search for documents, that considered antiviral therapies and contained a recommendations for clinicians. The quality of the guidelines was assessed using the AGREE II-Global Rating Scale Instrument and series of additional criteria. RESULTS: The analysis included 40 publications. The median of quality of documents assessed with the AGREE II-GRS tool was 2.0 (interquartile range 1.5-2.5). Most documents did not fulfill the rigour of guideline development quality criteria. The AGREE II-GRS scores did not differ significantly across the type of the document, issuing institution and the mode of publication. 75% of documents provided recommendations for the use of antiviral medications despite apparent lack of sufficient evidence supporting such treatments. Of the included documents, 75% were not updated within the 2 months after the publication of the first randomized controlled trial on COVID-19 antiviral therapy. CONCLUSIONS: Most guidelines or guidance documents published during the early phase of the COVID-19 pandemic were of poor quality, contained recommendations for the use of antiviral therapy for SARS-CoV-2 infection despite only very low quality of evidence available, and were not updated on a regular basis.

Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Heart Rate Variability in the Diagnostics and CPAP Treatment of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is the most common manifestation of sleep-related breathing disorders that are often accompanied by dysfunction of the autonomic nervous system. The main objective of the study was to assess the usefulness of heart rate variability (HRV) analysis in the diagnosis of patients with severe OSA and in the assessment of the effects of 3-month treatment with continuous positive airway pressure (CPAP). There were 54 patients enrolled in the study. The OSA group consisted of 39 patients suffering from severe OSA (apnea/hypopnea index >30/h), and the control group included 15 non-OSA patients with matched demographic characteristics and comorbidities. All patients underwent 24-h Holter electrocardiographic monitoring. HRV was analyzed using the time- and frequency-domains. We found that OSA patients had decreases in time-domains and increases in frequency-domains of HRV, compared to non-OSA controls, which strongly suggested a clinically disadvantageous shift in the balance of parasympathetic/sympathetic activity toward the latter. Further, CPAP treatment, partly, albeit significantly, reversed the OSA-induced changes in HRV. We conclude that HRV analysis may be of help in the diagnosis of OSA and in the monitoring of the effectiveness of treatment.

Prostaglandin E2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin.

BACKGROUND: A special regulatory role for prostaglandin E2 (PGE2 ) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). OBJECTIVE: To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA-CRSwNP), as well as healthy controls (HC). METHODS: Induced sputum (IS) was collected from patients with NERD (n = 26), ATA-CRSwNP (n = 17), and HC (n = 21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids, PGE2 , 8-iso-PGE2 , tetranor-PGE-M, 8-iso-PGF2 α, and leukotriene C4 , D4 , and E4 , were determined using mass spectrometry. Urinary excretion of LTE4 was measured by ELISA. RESULTS: NERD subjects had elevated sputum eosinophilic count as compared to ATA-CRSwNP and HC (median NERD 9.1%, ATA-CRSwNP 2.1%, and HC 0.4%; P < 0.01). Baseline ISS levels of PGE2 were higher in asthmatics as compared to HC at baseline (NERD vs HC P = 0.04, ATA-CRSwNP vs HC P < 0.05). Post-challenge ISS levels of PGE2 compared to baseline significantly decreased in NERD and HC (P < 0.01 and P = 0.01), but not in ATA-CRSwNP. In NERD, a similar decrease in PGE2 as in HC resulted from 2.8 times lower dose of aspirin. CONCLUSION: Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE2 biosynthesis. These results support the mechanism of PGE2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD.

Symptoms of chronic bronchitis in individuals without chronic obstructive pulmonary disease: prevalence, burden, and risk factors in southern Poland.

Introduction Chronic bronchitis (CB) symptoms are commonly reported in individuals without chronic obstructive pulmonary disease (COPD), but CB is rarely diagnosed in this population. Objectives We aimed to determine the prevalence and burden of CB, as well as its risk factors, in a population of patients without COPD. Patients and methods Data from the "Health Action" program (a lung cancer prevention and health care improvement program conducted in Proszowice County, Poland) were used. All county inhabitants aged 40 years or older without COPD were invited to participate. As part of the program, a questionnaire was administered to assess CB symptoms and risk factors. Spirometry at baseline and after the bronchodilator test was also performed. Results CB symptoms were present in 9.1% of the 3558 participants. The prevalence of CB in the study population was 7.12% (95% CI, 6.70-7.56). Patients with CB had more dyspnea and more often received medical treatment for lung disease or were hospitalized for respiratory disorders than patients without CB. CB was associated with worse lung function and a worse score in the modified Medical Research Council Dyspnea Scale even after adjustment for possible confounders. In a multivariate analysis, male sex, age over 70 years, current smoking, passive exposure to tobacco smoke, gas or wood heating, occupational exposure to chemical agents, lower forced expiratory volume in 1 second, and asthma correlated with an increased risk of CB. Conclusions CB symptoms are common in individuals without COPD aged 40 years or older and are associated with more dyspnea irrespective of lung function and comorbidities.

Advances in the treatment of mild asthma: recent evidence.

Asthma affects about 300 million individuals worldwide. Although most patients have mild disease, the majority of them do not have good control and are at risk of exacerbations. Poor compliance with regular maintenance treatment is a considerable problem and is believed to be the main reason for poor control in asthma. In patients with moderate to severe asthma, maintenance and as-needed treatment with one inhaler containing an inhaled corticosteroid (ICS) and the long-acting inhaled ß2-agonist formoterol has been proved effective in reducing the risk of severe exacerbations. Recently, the results of 2 large double-blind randomized trials assessing the use of as-needed budesonide/formoterol in patients with mild asthma, who had indications for a regular controller treatment, were published. In comparison with as-needed terbutaline treatment, as-needed budesonide/formoterol treatment improved symptom control and reduced the risk of exacerbations. In comparison with regular ICS treatment, exacerbation rates were similar, but regular treatment schedule was associated with better asthma control (despite a higher cumulative ICS dose). The results of these trials have shown that as-needed budesonide/formoterol therapy has acceptable efficacy in mild asthma and may be viewed as a therapeutic option for these patients. As-needed treatment may be preferred by patients who fear the side effects of ICS treatment or by those who experience difficulty in following a fixed-dose regimen. Patients with mild asthma wishing to achieve optimal asthma control may prefer regular maintenance treatment with an ICS.

Coexistence of Chronic Bronchitis in Chronic Obstructive Lung Disease.

The incidence of chronic obstructive pulmonary disease (COPD) is on the rise worldwide. Chronic bronchitis is a frequent accompaniment of COPD, which increases the burden of COPD in affected individuals. The aim of this study was to characterize the phenotype of chronic bronchitis in COPD patients. The study was based on the survey data retrospectively retrieved from the Action Health-Lung Cancer Prophylaxis and Health Care Improvement screening program that concerned all the inhabitants, aged over 40, of the Proszowice administrative region situated in the Lesser Poland Voivodeship in southern Poland. Participants with the symptoms suggestive of a lung disease were subject to further evaluation. The findings were that 546 (13.3%) out of the 4105 individuals displayed spirometry features of COPD. Symptoms of chronic bronchitis were present in 92 (16.8%) out of the COPD afflicted persons. Chronic bronchitis was commoner in current smokers and its incidence increased with increasing severity of airway obstruction. In multivariate analysis, chronic bronchitis was independently related to lower FEV1, FVC, FEV1/FVC, and to dyspnea. In regression model, factors related to increased risk of chronic bronchitis were current smoking, asthma, and lower lung function. We conclude that COPD with coexisting chronic bronchitis is linked to severer dyspnea and worse lung function. Current smoking, asthma, and lower lung function are related to increased risk of chronic bronchitis accompanying COPD.

Prevalence and burden of chronic bronchitis symptoms: results from the BOLD study.

We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.Representative population-based samples of adults aged ≥40 years were selected in participating sites. Participants completed questionnaires and spirometry. Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.Data from 24 855 subjects from 33 sites in 29 countries were analysed. There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi). Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis. Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.The prevalence of chronic bronchitis symptoms varied widely across the studied sites. Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.

Pulmonary prevention program in the Proszowice county: description and results.

INTRODUCTION: In the Proszowice county, both lung cancer and chronic obstructive pulmonary disease (COPD) are more common in comparison with other regions of Poland. The purpose of this study was to provide a report on a prevention program carried out in the area to reduce the burden of COPD and lung cancer in the region. MATERIAL AND METHODS: The program consisted of the following: active prevention - questionnaire survey offered to every county inhabitant aged at least 40 and chest X-ray and spirometry performed in selected subjects; and passive prevention - covering multiple educational activities promoting healthy lifestyle. Data obtained from questionnaire survey and spirometry were further analyzed. RESULTS: Education program covered all local children aged 13-15, a majority of adolescents and a significant proportion of adult inhabitants of the county. Questionnaire data were obtained from 14,455 subjects (about 70% of county inhabitants). On the basis of the questionnaire results, the participants were selected to undergo spirometry (5,816 subjects) and chest X-ray (5,514 subjects). Current smokers constituted 24.2% of the total number of participants (33.3% of men and 16.8% of women). Electronic cigarettes were currently used by 0.65% of the subjects. Negative impact of occupational exposures (including farming) on lung function and the presence of respiratory symptoms was observed. Basing on post-bronchodilator spirometry, COPD was diagnosed in 13.2% of the subjects. Physician's diagnosis of asthma was reported by 7.2%. CONCLUSION: Educational activities and questionnaire-based study were targeted at and reached the majority of the county inhabitants. The study provided data on the prevalence and risk factors of COPD, asthma and respiratory symptoms in the Proszowice region.

Severity of Airflow Obstruction in Chronic Obstructive Pulmonary Disease (COPD): Proposal for a New Classification.

Current classifications of Chronic Obstructive Pulmonary Disease (COPD) severity are complex and do not grade levels of obstruction. Obstruction is a simpler construct and independent of ethnicity. We constructed an index of obstruction severity based on the FEV1/FVC ratio, with cut-points dividing the Burden of Obstructive Lung Disease (BOLD) study population into four similarly sized strata to those created by the GOLD criteria that uses FEV1. We measured the agreement between classifications and the validity of the FEV1-based classification in identifying the level of obstruction as defined by the new groupings. We compared the strengths of association of each classification with quality of life (QoL), MRC dyspnoea score and the self-reported exacerbation rate. Agreement between classifications was only fair. FEV1-based criteria for moderate COPD identified only 79% of those with moderate obstruction and misclassified half of the participants with mild obstruction as having more severe COPD. Both scales were equally strongly associated with QoL, exertional dyspnoea and respiratory exacerbations. Severity assessed using the FEV1/FVC ratio is only in moderate agreement with the severity assessed using FEV1 but is equally strongly associated with other outcomes. Severity assessed using the FEV1/FVC ratio is likely to be independent of ethnicity.

Systemic prostacyclin and thromboxane production in obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea increases the risk of cardiovascular diseases. Alternations in prostacyclin and thromboxane concentrations and balance could constitute one of mechanisms linking sleep apnea and cardiovascular events. Thus we aimed to assess the concentrations of 6-keto-prostaglandin F1α (6-keto-PGF1α) (metabolite of prostacyclin) and thromboxane B2 (TXB2) (metabolite of thromboxane A2) in urine and blood of obstructive sleep apnea patients and controls (snoring subjects with otherwise normal polysomnogram). MATERIAL AND METHODS: Overnight urine and morning blood samples were taken from subjects and controls at baseline and in sleep apnea group during continuous positive airway pressure (CPAP) treatment. Samples were analyzed using mass chromatography/gas spectrometry. RESULTS: We analyzed data from 26 obstructive sleep apnea subjects (mean apnea-hypopnea index 45.4±17.3) and 22 well-matched controls. At baseline sleep apnea patients, when compared to controls, have higher 6-keto-PGF1α in urine (0.89±0.15 vs 0.34±0.06, p=0.01) and blood (24.49±1.54 vs 19.70±1.77, p=0.04). TXB2 levels in urine and blood were not different across groups. CPAP treatment significantly decreased 6-keto-PGF1α in urine (0.92±0.17 vs 0.22±0.10, p=0.04), but not in blood. TXB2 levels during CPAP treatment did not change significantly. CONCLUSIONS: These results suggest augmented systemic prostacyclin production in obstructive sleep apnea patients, which potentially could constitute a protective mechanism against detrimental effects of sleep apnea.

Clinical and biochemical factors for response to aspirin desensitization in aspirin-induced asthma patients ­ pilot study.

Aspirin desensitization is considered to be an effective and well-tolerated therapy for patients with Non-steroidal anti-inflammatory(NSAIDs)-Exacerbated Respiratory Disease (NERD). The aim of the present study was to investigate the influence of aspirin desensitization on inflammatory cell count in induced sputum and nasal lavage in fifteen NERD individuals subjected to one-year aspirin therapy. The decrease in induced sputum count of eosinophils and macrophages was observed. Clinical efficacy of aspirin therapy in improving nasal symptoms and quality of life in NERD patients was also confirmed.

Arterial and venous thromboembolism in chronic obstructive pulmonary disease: from pathogenic mechanisms to prevention and treatment.

Chronic obstructive pulmonary disease (COPD) affects approximately 10% of adults older than 40 years and is an important causes of disability and death in elderly subjects. A large proportion of COPD patients suffer from cardiovascular comorbidities. Thromboembolic events contribute considerably to morbidity and mortality in these subjects. This review summarizes the current evidence regarding the association of COPD with increased thromboembolic risk. We discuss multiple mechanisms potentially linking these conditions and available pharmacological interventions reducing the risk of thrombotic arterial and venous events with special attention paid to new oral anticoagulants.