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Chronic cough is a debilitating condition affecting 10-12% of the general population and is one of the leading causes for referral to secondary care. Many conditions have been associated with chronic cough, including asthma, gastro-esophageal reflux disease and upper airways cough syndrome. Inflammatory airway conditions including cough variant asthma (CVA) and non-asthmatic eosinophilic bronchitis (NAEB) contribute to a significant proportion of presentations with chronic cough, with differing diagnostic criteria and different responses to commonly used asthma therapy for their respective diagnoses. Mechanistic studies in both animal models and humans have identified increased neuronal sensitivity and subsequent central sensitization. These mechanisms include inflammatory-mediated nociceptor sensitization and alterations of afferent nerve terminal excitability, phenotypic changes in the vagal afferent neurons over time, and central neuroplasticity resulting from increased synaptic signalling from peripheral afferents. The aim of this review is to discuss the mechanisms, neurophysiology, and management approaches currently available for patients presenting with chronic cough with underlying asthma, CVA, and NAEB and to shed a light on areas of further research required to elucidate the mechanisms of cough in this patient population.

Impairment of pulmonary function was evaluated in chronic bronchitis patients with preserved ratio impaired spirometry (PRISm). We retrospectively collected clinical data from 157 chronic bronchitis (CB) and 186 chronic obstructive pulmonary disease (COPD) patients between October 2014 and September 2017. These patients were assigned to three groups: control (normal pulmonary function), PRISm (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ≥ 0.7, FEV1 p < 0.001 , maximal expiratory flow (MEF) 25% p < 0.001 , MEF50% p < 0.001 , maximal midexpiratory flow (MMEF) 25–75% p < 0.001 , residual volume (RV)/total lung capacity (TLC; p < 0.001 ), FVC% p < 0.001 , total respiratory resistance and proximal respiratory resistance (R5-R20; p < 0.001 ), respiratory system reactance at 5 Hz (X5; p < 0.001 ), resonant frequency (Fres; p < 0.001 ), and area of reactance (Ax; p < 0.001 ). However, the predicted FEV1% and RV/TLC were similar between the PRISm and COPD groups ( p = 0.992 and 0.122, respectively). PRISm is a nonspecific pattern of pulmonary function that indicates small airway dysfunction and may increase the risk of transformation to obstructive ventilation dysfunction. This trial is registered with ChiCTR-OCH-14004904.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD.Network analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CBA total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CBThe multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.

Until now, interventional therapies for patients with chronic obstructive pulmonary disease have been available in the form of lung volume reduction procedures as end-stage options. Currently, the range of indications is expanding to include earlier stages of the diseases. Lung denervation is available for moderate COPD, and patients with chronic bronchitis are being evaluated for endoscopic goblet cell ablation. Rheoplasty, metered spray cryo technique, and Karakoca resector balloon are used for this indication. But also, for patients with severe uncontrolled asthma, several techniques are available today. In addition to thermoplasty as a long-proven procedure, new and currently under investigation is the targeted lung denervation.Most of these techniques are currently being tested in large pivotal trials and it will soon become clear in which phenotype which technique will be used in the different forms and stages of obstructive diseases. The current paper presents the techniques and the currently available literature.

Objective. To analyze the risk factors of pulmonary infection in patients with type 2 diabetes mellitus (T2DM) and its implications for clinical intervention. Methods. One hundred and twenty-five patients with type 2 diabetes treated in our hospital from January 2019 to November 2021 were divided into simple T2DM group ( n = 80 ) and infection group ( n = 45 ) according to whether they were complicated with pulmonary infection or not. Sputum samples of patients with infection were collected and identified by bacterial culture. The general conditions (age, sex, body mass index, course of disease, and length of stay), pulmonary complications (chronic bronchitis, emphysema, and obstructive pulmonary disease,), blood glucose control (fasting blood glucose and glycosylated hemoglobin), and treatment (use of hormones and antibiotics and invasive operation) were compared between the two groups. Univariate and multivariate analyses were used to screen the risk factors of pulmonary infection in patients with T2DM. Results. A total of 45 patients were found to be infected in this study. 68 pathogenic bacteria were detected in the sputum samples, of which 42 were Gram-negative (61.76%), 22 were Gram-positive (35.35%), and 4 were fungi (5.88%). Gram-negative bacteria were mainly Klebsiella pneumoniae, accounting for 25.00%, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. Gram-positive bacteria were mainly Staphylococcus aureus, accounting for 17.65%, followed by Streptococcus pneumoniae and Staphylococcus haemolyticus. The main fungi were Candida albicans (4.41%). The age, the course of T2DM, and the duration of hospitalization in the coinfection group were significantly higher than those in the T2DM group ( P < 0.05 ). There was no significant difference in other indexes ( P > 0.05 ). The number of patients with chronic bronchitis, emphysema, and obstructive pulmonary disease in the coinfection group was significantly higher than that in the T2DM group. The fasting blood glucose and glycosylated hemoglobin in the coinfection group were significantly higher than those in the T2DM group. The number of patients using hormone and antimicrobial agents and invasive operation in the coinfection group was higher than that in the simple T2DM group, and the difference was statistically significant ( P < 0.05 ). Multivariate analysis showed that age, course of T2DM, length of hospital stay, complicated pulmonary disease, glycosylated hemoglobin, use of hormones and antibiotics, and invasive operation were all risk factors of pulmonary infection in patients with T2DM ( P < 0.05 ). Conclusion. Gram-negative bacteria are the main pathogens of T2DM complicated with pulmonary infection. Drug sensitivity test should be combined to understand the drug resistance of pathogenic bacteria and use drugs reasonably to patients. Among them, advanced age, long course of T2DM, long hospital stay, complicated pulmonary disease, high level of glycosylated hemoglobin, use of hormones and antibiotics, and invasive operation were all risk factors of pulmonary infection in patients with T2DM. In clinical treatment, under the premise of using insulin to control blood sugar in an appropriate range, antibiotics should be used reasonably, pulmonary complications should be treated actively, pulmonary ventilation function should be improved, and invasive operation should be avoided as far as possible, which can effectively prevent the occurrence of T2DM complicated with pulmonary infection.

Lower airway biofilms are hypothesised to contribute to poor treatment outcomes among children with chronic lung disease; however, data are scarce. We aimed to determine the presence and prevalence of biofilm in bronchoalveolar lavage from children with protracted bacterial bronchitis (PBB) or bronchiectasis; whether biofilm was associated with signs of lower airway infection; and whether biofilms were consistent with an upper or lower airway origin.In this cross-sectional study, fluorescent microscopy techniques were used to detect biofilm in archived bronchoalveolar lavage specimens from a paediatric cohort (age18 years) with PBB or bronchiectasis who were prospectively recruited to observational studies of chronic cough at Royal Children's Hospital (Brisbane, Australia) or Royal Darwin Hospital (Darwin, Australia). Children with cystic fibrosis were excluded. Lower airway infection was defined as bronchoalveolar lavage neutrophil percentage of 15% or more, or a culture of a bacterial pathogen at 10Biofilm testing was performed on 144 bronchoalveolar lavage specimens collected between Jan 1, 2011, and Dec 16, 2014, and preserved at -80°C before biofilm testing (69 children with PBB from Brisbane and 75 children with bronchiectasis from Darwin). The prevalence of lower airway biofilms (unrelated to squamous epithelial cells) was similar among the children with PBB (25 [36%] of 69) and children with bronchiectasis (31 [41%] of 75; odds ratio [OR] 1·24, 95% CI 0·63-2·43), but higher among children with signs of lower airway infection (46 [48%] of 95) than children without (eight [19%] of 43; OR 4·11, 95% CI 1·73-9·78), irrespective of the underlying diagnosis. By contrast, upper airway biofilms (associated with squamous epithelial cells) were more prevalent among children with bronchiectasis (32 [43%] of 75) than children with PBB (16 [23%] of 69; OR 2·47, 95% CI 1·20-5·08) and were unrelated to lower airway infection. Upper airway contamination was uncommon (eight [11%] of 71) and was not evident in 23 (79%) of 29 bronchoalveolar lavages that were positive for upper airway biofilms.Lower airway biofilms are prevalent, but not ubiquitous, in bronchoalveolar lavage from children with PBB or bronchiectasis, suggesting anti-biofilm therapies might be beneficial for some children. Detection of upper airway biofilms in bronchoalveolar lavage that did not have signs of contamination suggests that microaspiration might be important in some children. Specimen quality measures are recommended for future studies to account for the presence of upper airway biofilms.Financial Markets for Children Project Grant, National Health and Medical Research Council of Australia, Rebecca L Cooper Medical Research Foundation, Queensland Children's Hospital Foundation, and BrightSpark Foundation.

Racial and ethnic disparities in chronic obstructive pulmonary disease (COPD) are not well-studied. Our objective was to examine differences in limited COPD-related outcomes between three minority groups - African Americans (AAs), Hispanics, and American Indians (AIs) versus non-Hispanic Whites (NHWs), as the referent group, in separate cohorts. Separate cross-sectional evaluations were performed of three U.S.-based cohorts of subjects at risk for COPD: COPDGene Study with 6,884 NHW and 3,416 AA smokers; Lovelace Smokers’ Cohort with 1,598 NHW and 378 Hispanic smokers; and Mining Dust Exposure in the United States Cohort with 2,115 NHW, 2,682 Hispanic, and 2,467 AI miners. Prebronchodilator spirometry tests were performed at baseline visits using standard criteria. The primary outcome was the prevalence of airflow obstruction. Secondary outcomes were self-reported physician diagnosis of COPD, chronic bronchitis, and modified Medical Research Council dyspnea score. All minority groups had a lower prevalence of airflow obstruction than NHWs (adjusted ORs varied from 0.29 in AIs to 0.85 in AAs; p

BACKGROUND Patients with multiple comorbidities who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have a higher risk of mortality. However, treatment with mepolizumab may be a key factor in counteracting the risk of these comorbidities. We present a patient who had an uneventful recovery from coronavirus disease 2019 (COVID-19), despite having 5 independent risk factors for severe disease and increased mortality. CASE REPORT A 75-year-old man with a long-standing history of asthma, chronic bronchitis, coronary artery disease, and hypertension presented to the Emergency Department in November 2020 with a 4-day history of fever, chills, shortness of breath, cough, and fatigue. Six months prior to this presentation, the patient was hospitalized for severe chronic bronchitis and acute exacerbation of asthma. His medications included mepolizumab, aclidinium, ramipril, diltiazem, aspirin, albuterol sulfate, and micronized budesonide/micronized formoterol fumarate dihydrate. Physical examination was unremarkable, except for cardiopulmonary distress. Laboratory tests showed leucocytosis. His chest X-ray revealed infiltrates and interstitial edema in the lower lung fields. A PCR test for SARS-CoV-2 was positive. COVID-19 pneumonia was diagnosed, and the patient was admitted to the hospital, where he was treated with acetaminophen, amoxicillin, dexamethasone, and supplemental oxygen. The patient remained stable and was discharged from the hospital the following day. He was free of all symptoms after 21 days. CONCLUSIONS This case of a 75-year-old man who presented with mild COVID-19 supports the findings from other reports of improvement in clinical outcomes for some patients with asthma who received treatment with mepolizumab.

There is increasing evidence that sex hormones may impact the development of obstructive lung disease (OLD). Therefore, we studied the effect of bilateral oophorectomy (oophorectomy) on the development of OLD. Women were identified from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Data were collected using the Rochester Epidemiology Project records-linkage system. A total of 1653 women who underwent oophorectomy and 1653 referent women of similar age were assessed for OLD using diagnostic codes and medical record abstraction. Women who underwent oophorectomy had an overall higher risk of all OLD, all chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis but not of all asthma, confirmed asthma, or confirmed COPD. The association with all OLD was stronger in women who were age ≤45 years at oophorectomy, never smokers, non-obese, and in women with benign indications; however, the interactions were not statistically significant. There was an increased risk of all asthma in women age ≤45 years at oophorectomy who took estrogen therapy. Never smokers of all ages had a stronger association of oophorectomy with all asthma and all COPD, whereas smokers had a stronger association of oophorectomy with emphysema and chronic bronchitis. Non-obese women of all ages had a stronger association of oophorectomy with all COPD, emphysema, and chronic bronchitis. The results of this study combined with the increased risk of several chronic diseases reported in previous studies suggest that oophorectomy in premenopausal women should be avoided unless there is clear evidence of a high genetic risk of ovarian cancer.

Background The benefit of prompt vs delayed treatment initiation with inhaled long-acting bronchodilators in reducing exacerbations in chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate if long-acting bronchodilator therapy initiation within 30 days of COPD diagnosis reduces exacerbation risk in patients with COPD. Methods This was a retrospective cohort study of patients with COPD based on claims and electronic medical records data extracted from the Real World Data database. The index date (day 0) was the date of the first confirmed inpatient or outpatient COPD diagnosis between January 1, 2005, and December 31, 2018. Patients with COPD without an asthma diagnosis and aged ≥ 40 years at the index date were included. Patients who initiated inhaled long-acting bronchodilator therapy within the first 30 days (day 0 to day 29) were categorized into the “prompt therapy” group and the rest into the “delayed therapy” group. Time from day 30 post-diagnosis to the first exacerbation and annual exacerbation rate (AER) were evaluated for the overall population and those stratified by COPD phenotype, including chronic bronchitis (CB) and emphysema. Results Compared with the delayed therapy group (n = 1516), time to first exacerbation was prolonged (hazard ratio 0.78; 95% confidence interval [CI] [0.70, 0.87]) and annual rates of moderate or severe exacerbations were lower (rate ratio 0.74; 95% CI [0.65, 0.84]) in the prompt therapy group (n = 1466). Similarly, time to first exacerbation was prolonged and AERs were lower in the prompt therapy group in the subgroups of patients with CB or emphysema. Conclusions This is the first study to demonstrate a prolonged time to first exacerbation upon initiation of long-acting bronchodilators within 30 days of COPD diagnosis. A beneficial effect was also observed in patients with CB and emphysema. Our data support advising patients to initiate long-acting bronchodilators soon after COPD diagnosis.

Inhaled antibiotics reduce the frequency of exacerbations. The objective was to assess the efficacy of inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis (NCFB) and concomitant chronic bronchial infection (CBI) caused by potentially pathogenic microorganisms (PPM) other than Pseudomonas aeruginosa (PA).Quasi-experimental study in 21 patients with exacerbations who developed CBI by a PPM other than PA.Bacterial infection was resolved in 85.7% patients. Rehospitalizations, length of hospital stay, moderate exacerbations and blood levels of CRP decreased significantly. In addition, SGRQ questionnaire also decreased more than 4 points in 57.1% of the patients.The results suggest that inhaled ceftazidime in NCFB unrelated to PA is a plausible alternative to the standard therapies used in clinical practice.

Exposures to dust, vapors, or fumes (DVF) are associated with chronic bronchitis (CB) and emphysema. The 2007-2012 National Health and Nutrition Examination Survey data were used to estimate age-standardized prevalence of CB and emphysema among ever-employed adults by exposure status and industry and occupation groups. Age-standardized CB and emphysema prevalence were 2.3% and 1.9%, respectively. Of the estimated 111 million U.S. workers exposed to DVF, 2.7% reported CB and 2.8% reported emphysema. Workers in the "accommodation, food services" industry and "food preparation, serving related" occupations were more likely to report CB and emphysema. Current findings indicate that workplace exposures may be associated with high prevalence of CB and emphysema in certain industry and occupational groups. Early diagnosis and identifying associated workplace exposures are important steps in CB and emphysema prevention efforts.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are amongst the most common reasons for hospital admission, and recurrent episodes occur frequently. Comprehensive care management (CCM) strategies have modest effect in preventing re-admissions. The objectives of this study were to examine the utility of optimizing anti-inflammatory therapy guided by sputum cytometry in the post-hospitalization setting, and to assess the feasibility and effectiveness of a clinic combining CCM and sputum-guided therapy. This is an observational study examining patients who received open-label CCM and sputum cytometry-guided pharmacotherapy in a COPD post-discharge clinic. Referral was based on high risk for readmission after hospitalization for AECOPD. The primary outcome was the change in COPD-related healthcare utilization before and after Visit 1, and this was analyzed with a mixed-effects negative binomial model controlling for age, number of follow-up clinic visits, pack years, current smoking and FEV1. Of 138 patients referred to the clinic, 73% attended at least one visit. Mean FEV1 was 42.8 (19.3) % predicted. Of the patients attending clinic, 42.6% produced an adequate sputum sample, and 32.7% had an abnormal sputum. By individual, infectious bronchitis was the most common (25.7%), followed by eosinophilic bronchitis (13.9%). Comparing the 6-months prior to and after the first clinic visit, there was a lower incidence rate ratio after visit 1 for COPD-related healthcare utilization (0.26 (95%CI 0.22,0.33; p < 0.001)). A COPD post-discharge clinic combining sputum-guided treatment and CCM was feasible and associated with a nearly 75% reduction in the incidence of COPD-related healthcare utilization.

Theophylline is used in canine medicine for the management of chronic bronchitis and bradyarrhythmias, yet no species-validated commercial products are available. This study reports the single-dose and multidose pharmacokinetics and safety of a modified, compounded theophylline (MCT) product readily available from a well-established, USP-compliant compounding pharmacy, which may be a suitable and reliable source for theophylline for dogs. Eleven dogs underwent serial plasma theophylline measurement following 10 mg/kg MCT PO. After a 7 days washout, dogs received 10 mg/kg MCT PO q12h and serial plasma theophylline quantification was repeated after the ninth dose. Dogs were monitored for potential adverse effects. For the nine dogs that completed the study, plasma theophylline concentrations were between 5 and 30 μg/ml for 91 +/- 15% of the dosing interval. There was no significant difference in half-life between single-dose and multidose administration. The most common adverse effects reported were mild and included agitation, excitement, and increased activity. The results of this study support the use of 10 mg/kg MCT administered twice daily as a starting dosage in dogs. This regimen appears safe, achieves appropriate plasma drug concentrations in most dogs, and does not cause significant changes in pharmacokinetic properties at steady state. Because compounded drugs do not undergo consistent testing for identity, quality, strength, purity, and stability, results of research described in reports using compounded products may not be reproducible.

Background Chronic rhinosinusitis (CRS) is associated with generalised airway inflammation. Few studies have addressed the relationship between CRS and chronic bronchitis (CB). Methods This prospective study over a five-year period aims to investigate the risk of developing CB in subjects reporting CRS at the beginning of the study. A random sample of 7393 adult subjects from Telemark County, Norway, answered a comprehensive respiratory questionnaire in 2013 and then 5 years later in 2018. Subjects reporting CB in 2013 were excluded from the analyses. New cases of CB in 2018 were analysed in relation to having CRS in 2013 or not. Results The prevalence of new-onset CB in 2018 in the group that reported CRS in 2013 was 11.8%. There was a significant increase in the odds of having CB in 2018 in subjects who reported CRS in 2013 (OR 3.8, 95% CI 2.65–5.40), adjusted for age, sex, BMI, smoking and asthma. Conclusion In this large population sample, CRS was associated with increased odds of developing CB during a five-year follow-up. Physicians should be aware of chronic bronchitis in patients with CRS.

Chronic Obstructive Pulmonary Disease (COPD) and asthma are associated with chronic inflammation leading to airway obstruction and remodelling. There is little information on possible differences in the TGFB signalling pathway in the pathologies compared to less severe chronic bronchitis without airway obstruction.To assess the expression of the selected TGFB signalling pathway-associated genes in the pathologies.RT-PCR was used to quantify the mRNAs in bronchoalveolar cells obtained from the Czech patients with chronic bronchitis (n = 26), COPD (n = 22), asthmatic (n = 14) patients.There was no difference in the BAL cell expression of TGFB1-3, TGFBR1-2, SMAD2,4,5, and 7 between our patients with COPD and those with chronic bronchitis. The expressions were also similar in the patients with asthma and chronic bronchitis. There was no difference between the patients with asthma and COPD.Although we observed no differences in our patients, other studies should investigate the genes and their possible correlation with advanced airway obstruction and emphysematous changes (Tab. 2, Fig. 3, Ref. 27). Text in PDF www.elis.sk Keywords: TGFB signalling pathway, COPD, asthma, chronic bronchitis, bronchoalveolar lavage.

Basic lung and heart ultrasound examination combined with chest X-ray (TUSX) is currently considered to be very useful for differentiation of asthma, chronic bronchitis and laryngeal paralysis from other diseases with dyspnea/coughing. Among 252 client-owned animals with persistent dyspnea/cough/noisy breathing, in 197 of them: pulmonary edema, pneumonia, lung cancer, free pleural fluid, pneumothorax, lung contusion or heart disease were diagnosed. The remaining 55 animals (42 dogs and 13 cats) were diagnosed with asthma (in 13 cats), chronic bronchitis (in 37 dogs) and laryngeal paralysis (in 5 dogs) using TUSX. These animals were qualified for inhaled fluticasone treatment using 3 types of spacers - two commercial and a home- -made mask. 36 animals (65.5%) completed the trail. In 26 of them (72.2%) the owners observed complete, long lasting relief of the symptoms, and the owners of 7 animals (19.5%) declared a considerable clinical improvement, regardless of the type of spacer used. The owners of 3 animals (8.3%) did not see any improvement. The proposed diagnostic and therapeutic management improved long-term clinical status of the vast majority (91.7%) of animals. Therefore, it seems justified to include the TUSX diagnostic protocol in daily veterinary practice and to encourage owners to prepare home-made face masks for inhaled fluticasone treatment.

The aim of the work was to determine the concentration of low-molecular-weight plasma DNA (lmDNA) in patients with COPD and chronic non-obstructive bronchitis (CnonB) of two age groups - 34-59 and 60-80 years. The levels of lmDNA in healthy donors, patients with CnonB, healthy relatives of patients with COPD did not differ, while the concentration of lmDNA in patients with COPD was significantly lower. In COPD patients aged 34-59 years, the level of lmDNA was reduced by more than 7 times, and in COPD patients who survived to 60-80 years, it was 3 times lower compared to the value of this biochemical indicator in healthy donors of the same age. The reduction of lmDNA reflected a reduced systemic apoptotic activity in the body of patients with COPD. A significant difference in the concentration of lmDNA in patients with COPD and CnonB in remission can be used for differential diagnosis of the development of these pathological processes. An increase in the low level of lmDNA in COPD patients during aging may indicate the involvement of epigenetic mechanisms in life extension.Цель работы — определение концентрации низкомолекулярной ДНК (нмДНК) плазмы крови (нмДНК) у пациентов с ХОБЛ и хроническим необструктивным бронхитом (ХНБ) двух возрастных групп — 34–59 и 60–80 лет. Уровень нмДНК у здоровых доноров, больных ХНБ и здоровых родственников больных ХОБЛ в этих возрастных группах достоверно не различался. По сравнению с донорами, концентрации нмДНК у больных ХОБЛ были значительно ниже. Вместе с тем, у больных 34–59 лет c ХОБЛ уровень нмДНК был снижен более чем в 5 раз по сравнению с величиной биохимического показателя у одновозрастных здоровых родственников, но к 60–80 годам у больных значения биохимического параметра повышались и достоверно не различались в обследованных возрастных группах. Редукция нмДНК при ХОБЛ отражала сниженную системную апоптозную активность в организме больных. Значимые различия концентрации нмДНК у пациентов 34–59 лет с ХОБЛ и ХНБ в состоянии ремиссии могут быть использованы для дифференциальной диагностики развития этих патологических процессов. До 60–80 лет доживают больные ХОБЛ, у кого уровень нмДНК достигает такового у здоровых одновозрастных родственников, что может свидетельствовать об участии эпигенетических механизмов в процессе старения.

BackgroundOxidative stress plays a key role in the pathogenesis of respiratory diseases; however, studies on antioxidant vitamins and respiratory outcomes have been conflicting. We evaluated whether lower serum levels of vitamins A, C, D, and E are associated with respiratory morbidity and mortality in the U.S. adult population.MethodsWe conducted a pooled analysis of data from the 1988–1994 and 1999–2006 National Health and Nutrition Examination Survey (participants aged ≥ 20 years). We estimated covariate-adjusted odds ratios (aOR) per interquartile decrease in each serum vitamin level to quantify associations with respiratory morbidity, and covariate-adjusted hazard ratios (aHR) to quantify associations with respiratory mortality assessed prospectively through 2015. Vitamin supplementation and smoking were evaluated as potential effect modifiers.ResultsLower serum vitamin C increased the odds of wheeze among all participants (overall aOR: 1.08, 95% CI: 1.01–1.16). Among smokers, lower serum α-tocopherol vitamin E increased the odds of wheeze (aOR: 1.11, 95% CI: 1.04–1.19) and chronic bronchitis/emphysema (aOR: 1.13, 95% CI: 1.03–1.24). Conversely, lower serum γ-tocopherol vitamin E was associated with lower odds of wheeze and chronic bronchitis/emphysema (overall aORs: 0.85, 95% CI: 0.79–0.92 and 0.85, 95% CI: 0.76–0.95, respectively). Lower serum vitamin C was associated with increased chronic lower respiratory disease (CLRD) mortality in all participants (overall aHR: 1.27, 95% CI: 1.07–1.51), whereas lower serum 25-hydroxyvitamin D (25-OHD) tended to increase mortality from CLRD and influenza/pneumonia among smokers (aHR range: 1.33–1.75). Mortality from influenza/ pneumonia increased with decreasing serum vitamin A levels in all participants (overall aHR: 1.21, 95% CI: 0.99–1.48). In pooled analysis, vitamin C deficiency and 25-OHD insufficiency were associated with mortality from influenza/pneumonia, increasing mortality risk up to twofold.ConclusionsOur analysis of nationally representative data on over 34,000 participants showed that lower serum levels of vitamins A, C, D, and α-tocopherol vitamin E are associated with increased respiratory morbidity and/or mortality in U.S. adults. The results underscore the importance of antioxidant vitamins in respiratory health.

Background: Workers in the textile industry risk developing various respiratory and pulmonary diseases due to exposure to cotton dust. The particles from the cotton lint are inhaled by the workers and results in the breathing problems including asthma, shortness of breath, cough and tightness in the chest. The poor health of labor contributes to the low productivity of the labor and in serious cases loss of jobs leading to the poverty. Objective: To assess the prevalence of respiratory symptoms among the textile workers and associated community. To contrast the health profiles of the textile workers, associated community and the control group to factor out any confounding factors. Methods: This study explores the health profiles of the textile workers and associated community and contrast them against the health profile of the control group to factor out any confounding factors. The study is conducted on cotton industry in Kasur, Pakistan. We interviewed 207 workers, 226 people from associated community (living in vicinities of weaving units) and 188 people for control group (from areas far away from weaving units and people are not associated with weaving industry) based on stratified random sampling technique. We employed descriptive methods and logistic regression to explore the association between respiratory diseases and weaving workers. Results: Overall, prevalence of postnasal drip, byssinosis, asthma, and chronic bronchitis were 47%, 35%, 20%, and 10%, respectively, among the workers. These percentages are significantly higher than the control group. An additional year of work increase the risk of postnasal drip, byssinosis, asthma, and chronic bronchitis by 5–6%. Among workers, 43% and 21% feel difficulty in hearing against noisy background and at low volume, respectively. Due to bad light arrangements at workstations, 21% and 31% workers are suffering from myopia and hyperopia, respectively. Proportions of the workers suffering from continuous headache, skin infection, depression, and low back pain are 28%, 29%, 27%, and 44%, respectively. Chi-square test results confirms that no confounding factor like air pollution is involved in this cause-and-effect study implying the association between the cotton dust and associated diseases is not spurious. Conclusion: Respiratory symptoms were statistically significantly more common in the weaving workers compared to control group. Better environment at workstations, use of protective gears and education are the factors which reduce the risk of associated diseases among workers.

Anja Lærke Frederiksen,1 Birgitte Hamann Laustsen,2,3 Jesper Bælum,4 Michael Lynge Pedersen,1,3 Jakob Hjort Bønløkke5 1Steno Diabetes Center Greenland, Nuuk, Greenland; 2Department of Clinical Medicine, Faculty of Medicine, Danish Ramazzini Centre, Aalborg University, Aalborg, Denmark; 3Greenland Center for Health Research, Institute of Nursing and Health Science, University of Greenland, Nuuk, Greenland; 4Research Unit for General Practice, Department of Public Health, University of Southern Denmark, Odense, Denmark; 5Department of Occupational and Environmental Medicine, Danish Ramazzini Centre, Aalborg University Hospital, Aalborg, DenmarkCorrespondence: Jakob Hjort Bønløkke, Department of Occupational and Environmental Medicine, Danish Ramazzini Centre, Aalborg University Hospital, Havrevangen 1, Aalborg, 9000, Denmark, Tel + 45 97664109, Email jahb@rn.dkIntroduction: For decades, the prevalence of smoking has been high in Greenland. Even so, the prevalence of chronic obstructive pulmonary disease (COPD), a smoking-related disease, remains largely unexplored. This cross-sectional study aimed to estimate the prevalence of COPD and chronic bronchitis (CB) among Inuit workers in the seafood industry in Greenland.Methods: A total of 355 participants, 254 males and 101 females, met the inclusion criteria. Participants had a mean age of 38 years (standard deviation 13.5; range 17– 68 years). COPD was diagnosed based on post-bronchodilator ratio between forced expiratory volume within one second and forced vital capacity (FEV1/FVC) below the lower limit of normal (LLN) according to the Global Lung Function Initiative. Participants completed a questionnaire aiming to diagnose CB.Results: The overall prevalence was 9.9% for COPD; 7.4% for CB. Participants were predominantly smokers; 73.2% active smokers, 91.8% active or former smokers. The prevalence of COPD was high, especially among those under 40 years of age. Both COPD and CB were associated with smoking status.Discussion: This study among Greenlandic seafood workers found that smoking was a risk factor for COPD and CB among Greenlanders of Inuit origin. The high prevalence of COPD and the high prevalence of smoking underlines the importance of further initiatives to reduce smoking in Greenland.Keywords: chronic obstructive pulmonary disease, chronic bronchitis, Greenland, Inuit, smoking, lung function

Martina Sundqvist,1,* Kristina Andelid,2,* Ann Ekberg-Jansson,3 Johan Bylund,4 Anna Karlsson-Bengtsson,1,5 Anders Lindén6,7 1Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2COPD Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 5Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; 6Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 7Karolinska Severe COPD Center, Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden*These authors contributed equally to this workCorrespondence: Martina SundqvistDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, Gothenburg, S-413 46, SwedenEmail martina.sundqvist@rheuma.gu.sePurpose: The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations.Patients and Methods: The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth.Results: When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with HNS or LTS. Nor did this level of Galectin-3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations.Conclusion: Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting.Keywords: COPD, CRP, airflow limitation, exacerbation

BackgroundChronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB.MethodsIn smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0–4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit.Measurements and main resultsOf 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all pConclusionsHigher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.

Chronic obstructive pulmonary disease (COPD) patients with higher eosinophil counts are associated with increased clinical response to phosphodiesterase‐4‐inhibitors (PDE4i). However, the underlying inflammatory mechanisms associated with this increased response is not yet elucidated. This post hoc analysis focused on sputum gene expression in patients with chronic bronchitis who underwent 32‐day treatment with two doses of the inhaled PDE4i CHF6001 (tanimilast) or placebo on top of triple therapy. Biological characterization and treatment effects were assessed between patients with different sputum eosinophil levels (eosinophilhigh ≥ 3%; eosinophillow

Background Concerns about global climate change force local public health agencies to assess potential local disease risk. Objective Determine if risk of an emergency department chronic bronchitis diagnosis in Douglas County, NE, was higher during the 2012 heatwave compared to the same calendar period in 2011. Methods Retrospective, observational, case-control design selecting subjects from 2011 and 2012 emergency department (ED) admissions. Risk was estimated by conditional logistic regression. Results The odds of an ED chronic bronchitis diagnosis among females was 3.77 (95% CI =1.37-10.21) times higher during the 2012 risk period compared to females admitted to the ED during the 2011 risk period. Chronic bronchitis ED diagnosis odds were 1.05 (95%CI=1.04 – 1.06) times higher for each year of age. ED, gender, and race modified the risk (i.e., effect). The overall chronic bronchitis ED risk estimate was 1.61 (95%CI=0.81 – 3.21) times higher during the 2012 risk period compared to the 2011 risk period. The mean ambient absolute humidity upon admission was 11.44 gr/m3 (95%CI; 10.40 – 12.47) among chronic bronchitis cases and 12.67 gr/m3 (95%CI; 12.63 – 12.71) among controls. Conclusion The odds of ED chronic bronchitis diagnosis was higher among female subjects admitted during the 2012 risk period compared to females admitted during the 2011 risk period. Age also increased chronic bronchitis ED diagnosis risk among 2012 risk period admissions compared to 2011 risk period admissions.

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane. GCD was divided into tertiles based on log10 transformed values. Log10GCD was greater in current smokers compared to former smokers. Those with classically defined CB or SGRQ defined CB had a greater log10 GCD compared to those without CB. Current smoking was independently associated with tertile 3 (high log10GCD) whereas CB was not in multivariable regression when adjusting for lung function and demographics. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.

Domestic cleaners have an increased risk of asthma-like and other respiratory symptoms and conditions. Uncertainty exists about which products are most hazardous. We aimed to investigate, among professional domestic cleaners, the associations of ocular/respiratory outcomes with using specific types of products at work and with the ability to choose their own products. Among domestic cleaners employed by “service vouchers” companies in Belgium, we administered an online questionnaire on ocular/respiratory symptoms (frequency and time relation to workdays), frequency of use of 40 types of products, and ability to choose one’s own products. Work-relatedness was defined as symptoms improving/disappearing on days off-work. We studied associations between frequency of product-use with work-related outcomes (eye irritation, rhinitis symptoms, sore throat, laryngeal symptoms, asthma symptoms, cough) and with chronic bronchitis, using multivariable logistic and elastic net regression. Adjusted odds ratios (OR) with 95%-confidence intervals were obtained per time a product was used per week. Among 1,586 domestic cleaners (99% women), the number of times sprays were used (median 13/week) was significantly associated with all outcomes (ORs between 1.012 and 1.024 per time sprays were used per week). Bleach/disinfectant-containing liquid products were associated with all outcomes, except for laryngeal symptoms (ORs 1.086 to 1.150); ammonia with work-related upper airway symptoms and chronic bronchitis. Cleaners able to choose their own products had fewer work-related eye symptoms (OR 0.728;0.556–0.954), rhinitis (OR 0.735;0.571–0.946) and cough (OR 0.671;0.520–0.865). Using elastic net regression, work-related rhinitis was most strongly associated with mould removal spray (OR 1.108;1.006–1.248), carpet/seat/curtain spray (OR 1.099;1.001–1.304) and ammonia (OR 1.081;1.002–1.372); work-related asthma with carpet/seat/curtain spray (OR 1.103;1.017–1.322), mould removal spray (OR 1.029;0.995–1.199) and drain cleaner (OR 1.023;0.979–1.302). In a large group of domestic cleaners, we documented that cleaning products have a range of adverse respiratory effects. Empowering cleaners to choose their products may reduce the burden of symptoms. Domestic cleaners have an increased risk of asthma-like and other respiratory symptoms and conditions. Uncertainty exists about which products are most hazardous. We aimed to investigate, among professional domestic cleaners, the associations of ocular/respiratory outcomes with using specific types of products at work and with the ability to choose their own products. Among domestic cleaners employed by “service vouchers” companies in Belgium, we administered an online questionnaire on ocular/respiratory symptoms (frequency and time relation to workdays), frequency of use of 40 types of products, and ability to choose one’s own products. Work-relatedness was defined as symptoms improving/disappearing on days off-work. We studied associations between frequency of product-use with work-related outcomes (eye irritation, rhinitis symptoms, sore throat, laryngeal symptoms, asthma symptoms, cough) and with chronic bronchitis, using multivariable logistic and elastic net regression. Adjusted odds ratios (OR) with 95%-confidence intervals were obtained per time a product was used per week. Among 1,586 domestic cleaners (99% women), the number of times sprays were used (median 13/week) was significantly associated with all outcomes (ORs between 1.012 and 1.024 per time sprays were used per week). Bleach/disinfectant-containing liquid products were associated with all outcomes, except for laryngeal symptoms (ORs 1.086 to 1.150); ammonia with work-related upper airway symptoms and chronic bronchitis. Cleaners able to choose their own products had fewer work-related eye symptoms (OR 0.728;0.556–0.954), rhinitis (OR 0.735;0.571–0.946) and cough (OR 0.671;0.520–0.865). Using elastic net regression, work-related rhinitis was most strongly associated with mould removal spray (OR 1.108;1.006–1.248), carpet/seat/curtain spray (OR 1.099;1.001–1.304) and ammonia (OR 1.081;1.002–1.372); work-related asthma with carpet/seat/curtain spray (OR 1.103;1.017–1.322), mould removal spray (OR 1.029;0.995–1.199) and drain cleaner (OR 1.023;0.979–1.302). In a large group of domestic cleaners, we documented that cleaning products have a range of adverse respiratory effects. Empowering cleaners to choose their products may reduce the burden of symptoms. ispartof: Environment International vol:162 ispartof: location:Netherlands status: published

Miguel Angel Martinez-Garcia,1,2 Marc Miravitlles2,3 1Pneumology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 3Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainCorrespondence: Marc Miravitlles, Pneumology Department, Vall d’Hebron Barcelona Hospital Campus, P. Vall d’Hebron 119-129, Barcelona, 08035, Spain, Tel +34932746083, Email marcm@separ.esAbstract: Up to 50% of patients with chronic obstructive pulmonary disease (COPD) in stable state may carry potentially pathogenic microorganisms (PPMs) in their airways. The presence of PPMs has been associated with increased symptoms, increased risk and severity of exacerbations, a faster decline in lung function and impairment in quality of life. Although some clinical trials have demonstrated a reduction in exacerbations in patients chronically treated with systemic antibiotics, particularly macrolides, the selection of patients was based on the previous frequency of exacerbations and not on the presence of PPMs in their airways. Therefore, unlike in bronchiectasis, there is a lack of evidence-based recommendations for assessment and treatment of the presence of PPMs in either single or repeated isolations in COPD. In this article, we propose that chronic bronchial infection (CBI) in COPD be defined as the isolation of the same PPM in at least three sputum samples separated by more than one month; we review the impact of CBI on the natural course of COPD and suggest a course of action in patients with a single isolation of a PPM or suspected CBI. Antibiotic treatment in stable COPD should be recommended based on four main criteria: a) the presence of comorbid bronchiectasis, b) the demonstration of a single or multiple isolation of the same PPM, c) the clinical impact of CBI on the patients, and d) the type of PPM, either Pseudomonas aeruginosa or non-pseudomonal PPM. These recommendations are derived from evidence generated in patients with bronchiectasis and, until new evidence specifically obtained in COPD is available, they may help in the management of these challenging patients with COPD. Existing evidence suggests that inhaled therapy is insufficient to manage patients with moderate-to-severe COPD, frequent exacerbations, and CBI. New studies must be conducted in this particularly demanding population.Keywords: exacerbation, colonization, bronchial infection, Pseudomonas aeruginosa, bronchiectasis, pathogenic microorganisms

Background and objective Chronic obstructive pulmonary disease (COPD) patients with a body mass index (BMI) 2 are prone to develop adverse event of pharmacological treatment for frequent exacerbation. As chronic bronchitis (CB) is one of the strong risk factors of exacerbation, we investigated the associations between BMI and COPD exacerbations in patients with CB. Methods Patients with COPD were included from the Korean COPD Subgroup Study (KOCOSS), a multicenter observational cohort study. CB was defined using the St. George’s Respiratory Questionnaire and the participants were categorized according to BMI cut-off of 25 kg/m2. Exacerbations during a 1-year follow-up were compared among four groups: non-CB with BMI ≥ 25 kg/m2, non-CB with BMI 2, CB with BMI ≥ 25 kg/m2, and CB with BMI 2. Results Among the 1264 patients with COPD, 451 (35.7%) had CB and 353 (27.9%) had both CB and BMI 2. The COPD exacerbation risk increased across the non-CB with BMI 2, CB with BMI ≥ 25 kg/m2, and CB with BMI 2 groups (adjusted incidence rate ratio [95% confidence interval] 1.21 [0.89–1.62], 1.20 [0.77–1.88], and 1.41 [1.02–1.91], respectively, compared to the non-CB with BMI ≥ 25 kg/m2 group). Conclusions COPD patients having both CB and a BMI 2 are at higher risk of exacerbations. Considering that a BMI 2 often limits treatment options preventing exacerbations, modified guidelines might be needed for non-obese CB patients in Asia.

Primary ciliary dyskinesia (PCD) is a clinical syndrome characterized by cilia with an abnormal structure or function. Its main clinical manifestations comprise chronic bronchitis, cough, recurrent respiratory infections, situs inversus, and male infertility. Single-gene variants are widely assumed to be the main cause of this rare disease, and more than 40 genes have been described to be associated with its onset.This study investigated two unrelated Chinese patients diagnosed as PCD. The chest computed tomography scan was performed to identify PCD phenotypes of the two probands. Considering the effect of PCD on male fertility, routine semen analysis, sperm morphology examination, and scanning electron microscopy were performed to assess the semen characteristics of male proband in family 2 (F2 II-1), who had a history of infertility. Subsequently, the peripheral blood samples of probands were collected to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease.Whole-exome sequencing revealed a homozygousWe identified a homozygous variant reported previously and two compound heterozygous variants of

Purpose Managing and preventing disease exacerbations are key goals of COPD care. Oscillating positive expiratory pressure (OPEP) devices have been shown to improve clinical outcomes when added to COPD standard of care. This retrospective database study compared real-world resource use and disease exacerbation among patients with COPD or chronic bronchitis prescribed either of two commonly used OPEP devices. Patients and methods Patients using the Aerobika® (Trudell Medical International, London, ON, Canada) or Acapella® (Smiths Medical, Wampsville, New York, USA) OPEP device for COPD or chronic bronchitis were identified from hospital claims linked to medical and prescription claims between September 2013 and April 2018; the index date was the first hospital visit with an OPEP device. Severe disease exacerbation, defined as an inpatient visit with a COPD or chronic bronchitis diagnosis, and all-cause healthcare resource utilization over 30 days and 12 months post-discharge were compared in propensity score (PS)-matched Aerobika device and Acapella device users. Results In total, 619 Aerobika device and 1857 Acapella device users remained after PS matching. After discharge from the index visit, Aerobika device users were less likely to have ≥1 severe exacerbation within 30 days (12.0% vs 17.4%, p=0.01) and/or 12 months (39.6% vs 45.3%, p=0.01) and had fewer 12-month severe exacerbations (mean, 0.7 vs 0.9 per patient per year, p=0.01), with significantly longer time to first severe exacerbation than Acapella users (log-rank p=0.01). Aerobika device users were also less likely to have ≥1 all-cause inpatient visit within 30 days (13.9% vs 20.3%, p

Marni Stott-Miller,1 Hana Müllerová,2 Bruce Miller,3 Maggie Tabberer,4 Céline El Baou,5 Tom Keeley,4 Fernando J Martinez,6 Meilan Han,7 Mark Dransfield,8 Nadia N Hansel,9 Christopher B Cooper,10 Prescott Woodruff,11 Victor E Ortega,12 Alejandro P Comellas,13 Robert Paine III,14 Richard E Kanner,14 Wayne Anderson,15 M Bradley Drummond,15 Victor Kim,16 Ruth Tal-Singer,17 Aili L Lazaar3 1GSK R&D, Epidemiology: Value, Evidence and Outcomes, Uxbridge, UK; 2AstraZeneca, Cambridge, UK; 3GSK R&D, Discovery Medicine, Collegeville, PA, USA; 4GSK R&D Patient-Centred Outcomes: Value, Evidence and Outcomes, Uxbridge, UK; 5CEBSTAT Consultancy Ltd, London, UK; 6Cornell Medical College, New York, NY, USA; 7Division of Pulmonary and Critical Care at the University of Michigan, Ann Arbor, MI, USA; 8Children’s of Alabama, Children’s Health Research Unit/University of Alabama, Birmingham, AB, USA; 9Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA; 10David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 11UCSF Department of Medicine, San Francisco, CA, USA; 12Wake Forest School of Medicine, Winston Salem, NC, USA; 13Carver College of Medicine, University of Iowa, Iowa City, IA, USA; 14Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, UT, USA; 15Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 16Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; 17COPD Foundation, Washington, DC, USACorrespondence: Aili L Lazaar GSK, 1250 S. Collegeville Road, Collegeville, PA 19426-0989, USATel +1 484-923-3730Email Aili.L.Lazaar@gsk.comBackground: Chronic cough and phlegm are frequently reported chronic obstructive pulmonary disease (COPD) symptoms. Prior research classified chronic mucus hypersecretion (CMH) based on the presence of these symptoms for ≥ 3 months, called chronic bronchitis (CB) if respiratory infection symptoms were present for 1– 2 years (Medical Research Council [MRC] definition). We explored whether the COPD Assessment Test (CAT), a simple measure developed for routine clinical use, captures CMH populations and outcomes similarly to MRC and St. George’s Respiratory Questionnaire (SGRQ) definitions.Methods: We identified CMH in the SPIROMICS COPD cohort using (a) MRC definitions, (b) SGRQ questions for cough and phlegm (both as most/several days a week), and (c) CAT cough and phlegm questions. We determined optimal cut-points for CAT items and described exacerbation frequencies for different CMH definitions. Moderate exacerbations required a new prescription for antibiotics/oral corticosteroids or emergency department visit; severe exacerbations required hospitalization. Results were stratified by smoking status.Results: In a population of 1431 participants (57% male; mean FEV1% predicted 61%), 47% and 49% of evaluable participants had SGRQ- or CAT-defined CMH, respectively. A cut-point of ≥ 2 for cough and phlegm items defined CMH in CAT. Among SGRQ-CMH+ participants, 80% were also defined as CMH+ by the CAT. CMH+ participants were more likely to be current smokers. A higher exacerbation frequency was observed for presence of CMH+ versus CMH− in the year prior to baseline for all CMH definitions; this trend continued across 3 years of follow-up, regardless of smoking status.Conclusion: Items from the CAT identified SGRQ-defined CMH, a frequent COPD trait that correlated with exacerbation frequency. The CAT is a short, simple questionnaire and a potentially valuable tool for telemedicine or real-world trials. CAT-based CMH is a novel approach for identifying clinically important characteristics in COPD that can be ascertained in these settings.Keywords: COPD, SGRQ, exacerbation, CAT, cough, phlegm

Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease.

Farmers have an increased risk for chronic bronchitis and airflow obstruction. The objective of this study was to investigate the association of these health outcomes with farm activities.We evaluated the Keokuk County Rural Health Study (KCRHS) enrollment data for farm activities and the two health outcomes chronic bronchitis based on self-reported symptoms and airflow obstruction based on spirometry. We used logistic regression to model the health outcomes, yielding an odds ratio (OR) and 95% confidence interval (95% CI) for farm activities while adjusting for potential confounders and other risk factors.Of the 1234 farmers, 104 (8.4%) had chronic bronchitis, 75 (6.1%) fulfilled the criteria for airflow obstruction, and the two outcomes overlapped by 18 participants. Chronic bronchitis without airflow obstruction (n = 86) had a statistically significant association with crop storage insecticides (OR 3.1, 95% CI 1.6, 6.1) and a low number of years (≤ 3) worked with turkeys (OR 3.3, 95% CI 1.2, 9.4). The latter result should be interpreted with caution because it is based on a small number of cases (n = 5). Airflow obstruction with or without chronic bronchitis (n = 75) was significantly associated with ever working in a hog or chicken confinement setting (OR 2.2, 95% CI 1.0, 4.5).These results suggest that work with crop storage insecticides or turkeys may increase the risk for chronic bronchitis and work in hog or chicken confinement may increase the risk for airflow obstruction.

BackgroundChronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown.ObjectiveTo investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age.DesignCohort study from age 7 to 53 years.SettingGeneral population of European descent from Tasmania, Australia.Participants3202 participants of the age 53-year follow-up (mean age 53, range 51–55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis.Statistical methodsMultivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated.ResultsAmong 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: ‘non-recurrent bronchitis’ (28.1%); ‘recurrent non-protracted bronchitis’ (18.1%) and ‘recurrent-protracted bronchitis’ (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend ConclusionIn this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. ‘Recurrent-protracted bronchitis’, while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood ‘bronchitis’ into middle-age.

Metals, arsenic, and polycyclic aromatic hydrocarbons (PAHs) have all been linked to respiratory diseases. Chronic bronchitis, which is a form of chronic obstructive pulmonary disease (COPD), is a major public health concern and source of morbidity and mortality in the US. The purpose of this study was to analyze the correlation of 14 urinary metals (antimony, barium, cadmium, cesium, cobalt, lead, manganese, mercury, molybdenum, strontium, thallium, tin, tungsten, uranium), seven species of arsenic, and seven forms of polycyclic aromatic hydrocarbon (PAH) concentrations and chronic bronchitis in the US population. A cross-sectional analysis using three datasets from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 in adults, aged 20 years and older. Chronic bronchitis was determined using a self-questionnaire from the NHANES dataset. A specialized weighted complex survey design analysis package was used to analyze NHANES data. Multivariate logistic regression models were used to determine the correlation between urinary metals, arsenic, PAHs, and chronic bronchitis. Models were adjusted for lifestyle and demographic factors. A total of 4186 participants were analyzed; 49.8% were female and 40.5% were non-Hispanic White. All seven types of PAHs showed a positive association with chronic bronchitis (1-hydroxynaphthalene odds ratio (OR): 1.559, 95% confidence interval (CI): 1.271-1.912; 2-hydroxynaphthalene OR: 2.498, 95% CI: 1.524-4.095; 3-hydroxyfluorene OR: 2.752, 95% CI: 2.100-3.608; 2-hydroxyfluorene OR: 3.461, 95% CI: 2.438-4.914; 1-hydroxyphenanthrene OR: 2.442, 95% CI: 1.515-3.937; 1-hydroxypyrene OR: 2.828, 95% CI: 1.728-4.629; 23-hydroxyphenanthrene OR: 3.690, 95% CI: 2.309-5.896). Of the metals, only urinary cadmium showed a statistically significant positive association (OR: 2.435, 95% CI: 1.401-4.235) with chronic bronchitis. No other metals or arsenic were correlated with chronic bronchitis. Seven forms of urinary PAHs, cadmium, and several demographic factors were associated with chronic bronchitis.

Background. Patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis are associated with poor clinical outcomes. N-acetylcysteine (NAC) is a widely used therapeutic option for such patients; however, the clinical efficacy of NAC has not been conclusively determined. We hypothesized that high-dose oral NAC can improve the clinical outcomes for patients with concurrent chronic bronchitis and COPD. Objective and Methods. This was a randomized, double-blind, placebo-controlled trial evaluating the efficacy of high-dose NAC for COPD patients with concurrent chronic bronchitis. Study participants were randomized into two groups and administered with NAC (900 mg) twice daily or matching placebo for 3 months. Then, respiratory health status was evaluated using the St. George’s Respiratory Questionnaire (SGQR), which was set as the primary end point. Results. A total of 143 COPD patients with chronic bronchitis were screened, and as a result, only 100 patients were enrolled in this study (50 participants were randomized to receive placebo, and others were randomized to receive NAC). After treatment, differences in SGQR scores between the placebo and NAC groups were not significant. Moreover, differences in secondary end points between the two groups after treatment were insignificant. Discussion. High-dose NAC has no marked clinical benefits for COPD patients with concurrent chronic bronchitis.

International evidence has unveiled the existence of social inequalities in the risk of death associated with SARS-CoV-2 (COVID-19). In Portugal, the impossibility to identify the socioeconomic condition of deceased people hinders this evaluation. This study analyzes the social inequalities in the risk factors of COVID-19 mortality in Portugal.We used data from the sixth National Health Survey, carried out between September 2019 and December 2019, for the subgroup of people aged between 25 and 79 years old (n = 12 052). We considered the comorbidities with demonstrated link to COVID-19 mortality: asthma, chronic bronchitis, cardiovascular (CVD) and cerebrovascular disease, diabetes, hypertension, chronic renal disease (CRD), and obesity. The inequality, stratified by sex, was measured in terms of education and income, using logistic regression (odds ratios and relative index of inequality).Compared to men with the lowest level of formal education, we measured a risk reduction, among men with tertiary education, of CVD (-90%), chronic bronchitis (-75%), stroke (-70%), diabetes (-62%), hypertension (-41%), and obesity (-43%). Among tertiaryeducated women, we observed a reduced risk of CRD (-77%), hypertension, diabetes, stroke (-70%), obesity (-64%), and CVD (-55%). Except for obesity among men, the risk of disease was always significantly lower in the highest income quintile, compared with the lowest.In 2019, we observed socioeconomic inequalities of high magnitude for the eight diseases with demonstrated link to COVID-19 mortality.Introdução: A evidência internacional tem demonstrado desigualdades sociais no risco de morte por SARS-CoV-2 (COVID-19). Em Portugal, a impossibilidade de identificar a condição socioeconómica dos indivíduos falecidos impede esta medição. Este estudo analisa as desigualdades sociais nos fatores de risco de morte por COVID-19 em Portugal. Material e Métodos: Foram utilizados dados do sexto Inquérito Nacional de Saúde, conduzido entre setembro e dezembro de 2019, para pessoas entre 25 e 79 anos (n = 12 052). Foram consideradas as morbilidades com ligação demonstrada à morte por COVID-19: asma, bronquite crónica, doenças cardiovasculares (DCV) e cerebrovasculares (AVC), diabetes, hipertensão, doença renal crónica (DRC) e obesidade. A desigualdade, estratificada por sexo, foi medida em termos de educação e rendimento, através de regressões logísticas (odds ratios e índice relativo de desigualdade).Resultados: Em comparação com os homens com o nível de educação mais baixo, foi medido um risco inferior, para os homens com educação terciária, de DCV (-90%), bronquite crónica (-75%), AVC (-70%), diabetes (-62%), hipertensão (-41%) e obesidade (-43%). Nas mulheres com educação terciária, foi observada uma redução de risco de DRC (-77%), hipertensão, diabetes e AVC (-70%), obesidade (-64%) e DCV (-55%). Exceto no caso da obesidade nos homens, o risco de doença foi sempre estatisticamente inferior no quinto quintil de rendimento, comparado com o primeiro. Conclusão: Existiam, em 2019, desigualdades socioeconómicas de grande magnitude para oito doenças cuja ligação à mortalidade por COVID-19 foi amplamente identificada.

Aim This cross-sectional multicenter study was performed aimed at describing the clinical characteristics of women with COPD attended in routine daily practice in Spain. Methods and results Of a total of 1610 consecutive patients diagnosed with COPD recruited in primary care centers and pneumology services throughout Spain over a 90-day period, 17.9% (n=286) were women, with a median age of 62 years. Differences in COPD phenotypes by sex were statistically significant (P = 0.002). Males as compared with females showed a higher prevalence of non-exacerbator (47.9% vs 42.2%) and exacerbator with chronic bronchitis (22.9% vs 18.8%) phenotypes, whereas the ACOS phenotype was more common among females (21.7% vs 12.9%). The mean (SD) CAT score was similar in men than in women (20.8 [9.0] vs 21.2 [8.7], P = 0.481), as well as the impact of the disease on the quality of life according to CAT scores of 20 (high), and >30 (very high). Sex-related differences according to smoking status were statistically significant (P < 0.001), with a higher percentage of men as compared with women in the groups of current smokers and ex-smokers; never-smokers were higher in women (9.1%) than in men (0.6%). The mean number of comorbidities was 2.01 (1.43) (95% CI 1.93–2.09) in males and 1.99 (1.42) (95% CI 1.83–2.16) (P = 0.930) in females, but cardiovascular diseases (hypertension, ischemic heart disease, chronic heart failure) were more frequent in men, whereas metabolic disorders (osteoporosis) were more frequent in women. Conclusion This study highlights the impact of COPD in women and the importance of continuing sex-based research in tobacco-related respiratory diseases.

This study aims to explore the mechanism of fresh Phragmitis Rhizoma against chronic bronchitis airway inflammation. The SD rats of SPF grade were divided into control group, model group, Guilongkechuanning group(GLKCN, 1.125 g·kg~(-1)), high-dose fresh Phragmitis Rhizoma group(LG-HD, 15 g·kg~(-1)), and low-dose fresh Phragmitis Rhizoma group(LG-LD, 7.5 g·kg~(-1)). The chronic bronchitis models of rats in other groups except the control group were induced by the modified smoking method. From the 15 th day of modeling, the rats were given corresponding agents by gavage for 20 consecutive days. After the last administration, the rats were sacrificed for sample collection. Enzyme-linked immunosorbent assay(ELISA) was employed to detect serum transforming growth factor-β(TGF-β) and interleukin-6(IL-6) levels. The protein expression of TGF-β, IL-1β and IL-6 in lung tissue was detected by immunohistochemical method. Masson staining was performed to detect collagen fibers and muscle fibers in lung tissue, and HE staining to detect the pathological changes of lung tissue. Human bronchial epithelial(16 HBE) cells were cultured in vitro, and CCK-8(cell counting kit-8) method was used to detect the cytotoxicity of cigarette smoke extract(CSE) and fresh Phragmitis Rhizoma. After the exposure of 16 HBE cells to 3.5% CSE and appropriate concentration(800, 400 μg·mL~(-1)) of fresh Phragmitis Rhizoma for 24 h, quantitative real-time PCR was conducted to determine the mRNA levels of TGF-β and IL-1β, and Western blot was employed to determine the protein levels of TGF-β and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-β and IL-6 levels, down-regulated the protein levels of TGF-β, IL-1β, and IL-6 in lung tissue, and alleviated pathological changes and fibrotic lesions in lung tissue. Moreover, it down-regulated the CSE-induced protein expression of TGF-β and IL-6 as well as the mRNA level of TGF-β in 16 HBE cells. These results indicated that fresh Phragmitis Rhizoma could prevent airway inflammation from chronic bronchitis and promote cell repair by inhibiting the TGF-β signaling pathway.

Background Chronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores. Methods This study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score 1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB. Results Among the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB. Conclusions CB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

Eun Kyung Kim,1 Mi-Ae Kim,1 Jae Seung Lee,2 Sang Min Lee,3 Soyeoun Lim,4 Jisoo Park,1 Jung-Hyun Kim,1 Yeon-Mok Oh,2 Sang-Do Lee,2 Se Hee Lee,1 Ji-Hyun Lee1 On behalf of the KOLD Study Group1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of KoreaCorrespondence: Ji-Hyun LeeDepartment of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of KoreaTel +82-31-780-5205Fax +82-31-780-2992Email plmjhlee@cha.ac.krPurpose: Bronchiectasis (BE) is a poor prognostic factor in COPD. However, it is not clear whether the poor prognosis is a result of BE alone or accompanying chronic bronchitis symptoms. Therefore, we investigated the effect of chronic bronchitis symptoms on clinical outcomes in COPD patients with BE.Patients and Methods: We analyzed data of COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. The presence of BE was verified by chest computed tomography. Chronic bronchitis symptoms were determined using items in the symptomatic domain of the SGRQ, which is also used as an alternative definition of chronic bronchitis (CB). Patients were divided into four groups according to the presence of BE and CB symptoms: BE/CB, BE-only, CB-only, and no BE/CB. Demographic features and clinical outcomes were compared among these groups.Results: In total, 389 COPD patients were included in the analysis. BE was present in 148 (38%) patients and CB symptoms were found in 123 patients (33.2%). The patients were divided according to BE and CB symptoms, and the numbers and percentages of each group were as follows: BE/CB, 52 (13.4%); BE-only, 96 (24.7%); CB-only, 77 (19.8%); no BE/CB, 164 (42.2%). No significant differences were observed in baseline characteristics of lung function, radiological findings, and inflammatory markers among the four groups. The proportion of annual exacerbators was higher in the BE/CB and CB-only groups than the other two groups. After adjusting other parameters, the BE/CB group was significantly associated with acute exacerbation of COPD (AE-COPD) (OR = 2.110, p = 0.045).Conclusion: BE accompanying CB symptoms is associated with AE-COPD, while BE alone was not significantly associated. This finding suggests that it is more important to examine chronic bronchitis symptoms of BE to predict acute exacerbation than simply to identify BE in COPD patients.Keywords: COPD, bronchiectasis, chronic bronchitis, exacerbation

Introduction Aerosol pollutants are known to raise the risk of development of non-communicable respiratory diseases (NCRDs) such as asthma, chronic bronchitis, chronic obstructive pulmonary disease, and allergic rhinitis. Sub-Saharan Africa’s rapid pace of urbanization, economic expansion, and population growth raise concerns of increasing incidence of NCRDs. This research characterizes the state of research on pollution and NCRDs in the 46 countries of Sub-Saharan Africa (SSA). This research systematically reviewed the literature on studies of asthma; chronic bronchitis; allergic rhinitis; and air pollutants such as particulate matter, ozone, NOx, and sulfuric oxide. Methods We searched three major databases (PubMed, Web of Science, and Scopus) using the key words “asthma”, “chronic bronchitis”, “allergic rhinitis”, and “COPD” with “carbon monoxide (CO)”, “sulfuric oxide (SO)”, “ozone (O3)”, “nitrogen dioxide (NO2)”, and “particulate matter (PM)”, restricting the search to the 46 countries that comprise SSA. Only papers published in scholarly journals with a defined health outcome in individuals and which tested associations with explicitly measured or modelled air exposures were considered for inclusion. All candidate papers were entered into a database for review. Results We found a total of 362 unique research papers in the initial search of the three databases. Among these, 14 met the inclusion criteria. These papers comprised studies from just five countries. Nine papers were from South Africa; two from Malawi; and one each from Ghana, Namibia, and Nigeria. Most studies were cross-sectional. Exposures to ambient air pollutants were measured using spectrometry and chromatography. Some studies created composite measures of air pollution using a range of data layers. NCRD outcomes were measured by self-reported health status and measures of lung function (spirometry). Populations of interest were primarily schoolchildren, though a few studies focused on secondary school students and adults. Conclusions The paucity of research on NCRDs and ambient air pollutant exposures is pronounced within the African continent. While capacity to measure air quality in SSA is high, studies targeting NCRDs should work to draw attention to questions of outdoor air pollution and health. As the climate changes and SSA economies expand and countries urbanize, these questions will become increasingly important.