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.

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.

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.

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.

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.

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.

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.

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.

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.

Methodological rigor and reporting of clinical practice guidelines in patients with allergic rhinitis: QuGAR study.

BACKGROUND: There are several clinical practice guidelines about the management of allergic rhinitis (AR) being used by clinicians. OBJECTIVE: We sought to assess the methodological rigor and transparency of reporting of clinical practice guidelines for the management of AR. METHODS: We systematically searched MEDLINE, the TRIP database, and professional society Web sites for all guidelines about the management of AR published in English after the year 2000. Four reviewers independently assessed the rigor of development and reporting of included guidelines using the Appraisal of Guidelines for Research and Evaluation II instrument. RESULTS: Our search revealed 432 records, of which 34 full-text articles were assessed for eligibility and 10 fulfilled inclusion criteria. Overall methodological rigor and reporting of guidelines varied from fulfilling most of the Appraisal of Guidelines for Research and Evaluation II criteria to almost none. Across all guidelines, the best reported domain was clarity of presentation, and the least rigorously addressed domain was applicability of guidelines. Agreement beyond chance among the 4 appraisers was fair. CONCLUSIONS: Guideline users should be aware of the difference in the rigor of development and quality of reporting of guidelines about the management of AR. They should choose higher-quality guidelines to use in their practice and teaching. For most reviewed guidelines, there is room for improvement, particularly in the domains of applicability and implementation.

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.

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.

Case-finding options for COPD: results from the Burden of Obstructive Lung Disease study.

This study aimed to compare strategies for chronic obstructive pulmonary disease (COPD) case finding using data from the Burden of Obstructive Lung Disease study. Population-based samples of adults aged ≥40 yrs (n = 9,390) from 14 countries completed a questionnaire and spirometry. We compared the screening efficiency of differently staged algorithms that used questionnaire data and/or peak expiratory flow (PEF) data to identify persons at risk for COPD and, hence, needing confirmatory spirometry. Separate algorithms were fitted for moderate/severe COPD and for severe COPD. We estimated the cost of each algorithm in 1,000 people. For moderate/severe COPD, use of questionnaire data alone permitted high sensitivity (97%) but required confirmatory spirometry in 80% of participants. Use of PEF necessitated confirmatory spirometry in only 19-22% of subjects, with 83-84% sensitivity. For severe COPD, use of PEF achieved 91-93% sensitivity, requiring confirmatory spirometry in <9% of participants. Cost analysis suggested that a staged screening algorithm using only PEF initially, followed by confirmatory spirometry as needed, was the most cost-effective case-finding strategy. Our results support the use of PEF as a simple, cost-effective initial screening tool for conducting COPD case-finding in adults aged ≥40 yrs. These findings should be validated in real-world settings such as the primary care environment.

Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study.

RATIONALE: Criteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns. METHODS: 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airflow obstruction. RESULTS: In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (ΔFEV(1)); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV(1i)); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV(1p)). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVC(i)); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVC(p)). The proportion who exceeded the above threshold values in the subgroup with spirometrically defined Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV(1)/FVC <0.7 and FEV(1)% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV(1)-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds. CONCLUSIONS: The results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing.

[Effects of biomass combustion and occupational exposures on lung function in random population sample of Malopolska inhabitants]. / Wplyw spalania biomasy i narazen zawodowych na czynnosc pluc w losowej próbie populacyjnej mieszkanców Malopolski.

INTRODUCTION: Risk factors other than tobacco smoking contribute to about 20% of chronic obstructive pulmonary disease cases. Exposure to these risk factors and their influence on lung function has not been adequately studied in the population of Malopolska. MATERIAL AND METHODS: In random population sample of adults at least forty years old, residents of 2 districts of Malopolska, data on exposure to known and probable respiratory risk factors were collected using questionnaire. All subjects without contraindications performed pre- and post-bronchodilatator spirometry. RESULTS: We analyzed data from 618 subjects; 94,8% subjects lived for longer than 6 months in a dwelling where stove using coal or wood has been used for cooking and/or heating. At the time of study as many as 32.5% subjects were still using coal or wood for cooking or heating. Coal or wood were used as fuel on average for more than 30 years; 67% of subjects have ever worked in professions carrying a risk of exposure to potential respiratory risk factors. We have identified an independent relationship of farming with lower FEV1/FVC values as well as increased chronic obstructive pulmonary disease risk. CONCLUSIONS: Significant proportion of Malopolska inhabitants has been exposed to risks associated with cooking or heating with coal or wood. In the studied population farming was related to increased risk of chronic obstructive respiratory disease.

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.

The safety of long-acting beta-agonists among patients with asthma using inhaled corticosteroids: systematic review and metaanalysis.

RATIONALE: Inhaled long-acting beta-agonists (LABAs), when used as monotherapy in asthma, may increase asthma-related hospitalizations, life threatening events requiring intubation/mechanical ventilation, and asthma-related deaths, but concomitant use of inhaled corticosteroids (ICS) may modify this effect. OBJECTIVES: To determine the safety of long-acting beta-agonists among patients with asthma using corticosteroids. METHODS: We conducted a systematic review and metaanalysis of parallel-group, blinded, randomized, controlled trials with at least 12 weeks of treatment addressing the impact of LABA on asthma-related and total morbidity and mortality in patients concomitantly using ICS. We searched MEDLINE, EMBASE, ACPJC, and Cochrane (Central) databases, and contacted authors and sponsors. MEASUREMENTS AND MAIN RESULTS: We used a random effects model to pool results from different studies as odds ratios (ORs) (95% confidence interval [CI]) (OR < 1.0 favors LABA). The search yielded 62 relevant studies included in this analysis. Among over 29,000 participants (15,710 taking LABA, with over 8,000 patient-years observed in the LABA groups), there were three asthma-related deaths and two asthma-related, nonfatal intubations (all in LABA groups;

[Outpatients specialist care of chronic obstructive pulmonary disease patients in Poland - results of the KOMPAS study]. / Charakterystyka ambulatoryjnej opieki specjalistycznej nad choryni na przewlekla chorobe pluc w Polsce -- wyniki badania KOMPAS.

INTRODUCTION: COPD is one of the most important lung diseases. It is responsible for significant proportion of outpatients pulmonary clinics visits. Data on outpatients care of COPD patients in Poland are limited. This article presents design of the KOMPAS study and basic results relating to COPD patients. MATERIAL AND METHODS: The aim of this prospective study was to describe population of patients with COPD treated by specialists, and to characterize methods of care used in various COPD stages. Participating physicians used pocket PCs equipped with specially developed software to collect COPD patients' data. RESULTS: Data on 2958 COPD patients were analyzed. 2/3 of patients were males. Mean patients age was 63 years and mean FEV(1) - 57% of predicted value. 86% of all subjects underwent spirometry during the first visit or the previous 6 months. Cough and exertional dyspnoea were the most frequently reported COPD symptoms (about 80% of patients). At the first visit 32% of subjects were current smokers and 51% were ex-smokers. 17% of all study patients have never smoked. Before inclusion 2/3 of patients were treated with bronchodilatator, and about 1/3 with inhaled steroid. After entering the study, over 90% received bronchodilatator and more than 2/3 received inhaled steroid. Differences in treatment between stages of COPD based on its severity were relatively small. CONCLUSIONS: Results of the KOMPAS study provide basic information about COPD outpatients care in Poland. These data, especially concerning physicians' compliance with current COPD guidelines, may be useful in planning undergraduate/postgraduate training for physicians and for those who are responsible for health resource allocation.