Association of body mass index and COPD exacerbation among patients with chronic bronchitis.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) patients with a body mass index (BMI) < 25 kg/m2 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 < 25 kg/m2, CB with BMI ≥ 25 kg/m2, and CB with BMI < 25 kg/m2. RESULTS: Among the 1264 patients with COPD, 451 (35.7%) had CB and 353 (27.9%) had both CB and BMI < 25 kg/m2. The COPD exacerbation risk increased across the non-CB with BMI < 25 kg/m2, CB with BMI ≥ 25 kg/m2, and CB with BMI < 25 kg/m2 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 < 25 kg/m2 are at higher risk of exacerbations. Considering that a BMI < 25 kg/m2 often limits treatment options preventing exacerbations, modified guidelines might be needed for non-obese CB patients in Asia.

Chronic bronchitis in the 50-year follow-up of the European cohorts of the Seven Countries Study: prevalence, mortality and association with cardiovascular diseases.

OBJECTIVES: To study prevalence of chronic bronchitis (CB) in residential populations and its relationship with mortality in a 50-year follow-up. MATERIAL AND METHODS: In the late 1950's-early 1960's, 7047 men aged 40-59 years were enrolled in 10 European cohorts of the Seven Countries Study (in Finland, the Netherlands, Italy, Serbia and Greece). After baseline examination, follow-up for mortality was extended during 50 years (45 year in the Serbian cohorts). Prevalence of CB, and 50-year mortality from CB and other major causes of death were used as end-points to identify their determinants using multivariate models. RESULTS: Prevalence of CB was directly associated with smoking habits and inversely associated with high socio-economic status (SES), forced expiratory volume in ¾ sec (FEV) and the ratio FEV/vital capacity (VC). Fifty-year mortality from CB was directly predicted by CB prevalence (from a minimum hazard ratio [HR] 2.35, 95% confidence limits [CI] 1.70-3.24, to a maximum HR 3.01, CI 2.18-5.20, depending on diagnostic criteria and different models) and age, and inversely by high SES, FEV and FEV/VC. The same applied in models predicting mortality from coronary heart disease (HR for prevalent CB: 1.53, CI 1.24-1.88), major cardiovascular diseases (HR 1.43, CI 1.23-1.67) and all-cause mortality (HR 1.48, CI 1.34-1.64) all adjusted for age, high SES, smoking habits and FEV. CONCLUSIONS: CB is strongly associated with major cardiovascular disease and all-cause mortality while FEV and FEV/VC seem to carry at least partly an independent role from CB in predicting long-term mortality.

Association of Triglyceride-Glucose Index and Lung Health: A Population-Based Study.

BACKGROUND: Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown. RESEARCH QUESTION: What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function? STUDY DESIGN AND METHODS: This study analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2012. Participants included fasting adults age ≥ 40 years (N = 6,893) with lung function measurements in a subset (n = 3,383). Associations of TyG with respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), and lung function (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated, adjusting for sociodemographic variables, comorbidities, and smoking. TyG was compared vs insulin resistance, represented by the homeostatic model assessment of insulin resistance (HOMA-IR), and vs the metabolic syndrome. RESULTS: TyG was moderately correlated with HOMA-IR (Spearman ρ = 0.51) and had good discrimination for metabolic syndrome (area under the receiver-operating characteristic curve, 0.80). A one-unit increase in TyG was associated with higher odds of cough (adjusted OR [aOR], 1.28; 95% CI, 1.06-1.54), phlegm production (aOR, 1.20; 95% CI, 1.01-1.43), wheeze (aOR, 1.18; 95% CI, 1.03-1.35), exertional dyspnea (aOR, 1.21; 95% CI, 1.07-1.38), and a diagnosis of chronic bronchitis (aOR, 1.21; 95% CI, 1.02-1.43). TyG was associated with higher relative risk of a restrictive spirometry pattern (adjusted relative risk ratio, 1.45; 95% CI, 1.11-1.90). Many associations were maintained with additional adjustment for HOMA-IR or metabolic syndrome. INTERPRETATION: TyG was associated with respiratory symptoms, chronic bronchitis, and a restrictive spirometry pattern. Associations were not fully explained by insulin resistance or metabolic syndrome. TyG is a satisfactory measure of metabolic dysfunction with relevance to pulmonary outcomes. Prospective study to define TyG as a biomarker for impaired lung health is warranted.

Expression Profiling Suggests Loss of Surface Integrity and Failure of Regenerative Repair as Major Driving Forces for Chronic Obstructive Pulmonary Disease Progression.

Chronic obstructive pulmonary disease (COPD) poses a major risk for public health, yet remarkably little is known about its detailed pathophysiology. Definition of COPD as nonreversible pulmonary obstruction revealing more about spatial orientation than about mechanisms of pathology may be a major reason for this. We conducted a controlled observational study allowing for simultaneous assessment of clinical and biological development in COPD. Sixteen healthy control subjects and 104 subjects with chronic bronchitis, with or without pulmonary obstruction at baseline, were investigated. Using both the extent of and change in bronchial obstruction as main scoring criteria for the analysis of gene expression in lung tissue, we identified 410 genes significantly associated with progression of COPD. One hundred ten of these genes demonstrated a distinctive expression pattern, with their functional annotations indicating participation in the regulation of cellular coherence, membrane integrity, growth, and differentiation, as well as inflammation and fibroproliferative repair. The regulatory pattern indicates a sequentially unfolding pathology that centers on a two-step failure of surface integrity commencing with a loss of epithelial coherence as early as chronic bronchitis. Decline of regenerative repair starting in Global Initiative for Chronic Obstructive Lung Disease stage I then activates degradation of extracellular-matrix hyaluronan, causing structural failure of the bronchial wall that is only resolved by scar formation. Although they require independent confirmation, our findings provide the first tangible pathophysiological concept of COPD to be further explored.Clinical trial registered with www.clinicaltrials.gov (NCT00618137).

Structural airway imaging metrics are differentially associated with persistent chronic bronchitis.

BACKGROUND: Chronic 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. METHODS: In 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 RESULTS: Of 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 p<0.001). On follow-up of 5517 participants at 5 years, 399 (7.2%) had persistent CB. With adjustment for between-visits changes in smoking status and lung function, greater WA% and Pi10 were associated with significantly associated with persistent CB, adjusted OR per SD change 1.75, 95% CI 1.56 to 1.97; p<0.001 and 1.66, 95% CI 1.42 to 1.86; p<0.001, respectively. Higher AFD and TAC were associated with significantly lower odds of persistent CB, adjusted OR per SD change 0.76, 95% CI 0.67 to 0.86; p<0.001 and 0.69, 95% CI 0.60 to 0.80; p<0.001, respectively. CONCLUSIONS: Higher 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.

Clinical phenotypes and heath-related quality of life of COPD patients in a rural setting in Malaysia - a cross-sectional study.

BACKGROUND: The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients' health-related quality of life (HRQoL) according to their COPD phenotypes. METHODS: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c). RESULTS: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p <  0.001). There were significantly more patients with mMRC 2-4 among AE (68.6%) (p <  0.001), compared to those with ACO (38.5%) and NON-AE (16.7%). AE patients had significantly higher total CAT (p = 0.003; p <  0.001) and SGRQ-c (both p <  0.001) scores than those with ACO and NON-AE. Patients with ACO had significantly higher total CAT and SGRQ-c (both p <  0.001) scores than those with NON-AE. AE patients had significantly higher score in each item of CAT and component of SGRQ-c compared to those with NON-AE (all p <  0.001), and ACO [(p = 0.003-0.016; p = < 0.001-0.005) except CAT 1, 2 and 7. ACO patients had significantly higher score in each item of CAT and component of SGRQ-c (p = < 0.001-0.040; p <  0.001) except CAT 2 and activity components of SGRQ-c. CONCLUSIONS: The HRQoL of COPD patients was significantly different across different COPD phenotypes. HRQoL was worst in AE, followed by ACO and NON-AE. This study supports phenotyping COPD patients based on their exacerbation frequency and COPD subtypes. The treatment of COPD should be personalised according to these two factors.

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models.

The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channel expressed on capsaicin-sensitive afferents, immune and endothelial cells is activated by inflammatory mediators and exogenous irritants, e.g., endotoxins, nicotine, crotonaldehyde and acrolein. We investigated its involvement in acute and chronic pulmonary inflammation using Trpa1 gene-deleted (Trpa1-/-) mice. Acute pneumonitis was evoked by intranasal Escherichia coli endotoxin (lipopolysaccharide: LPS) administration, chronic bronchitis by daily cigarette smoke exposure (CSE) for 4 months. Frequency, peak inspiratory/expiratory flows, minute ventilation determined by unrestrained whole-body plethysmography were significantly greater, while tidal volume, inspiratory/expiratory/relaxation times were smaller in Trpa1-/- mice. LPS-induced bronchial hyperreactivity, myeloperoxidase activity, frequency-decrease were significantly greater in Trpa1-/- mice. CSE significantly decreased tidal volume, minute ventilation, peak inspiratory/expiratory flows in wildtypes, but not in Trpa1-/- mice. CSE remarkably increased the mean linear intercept (histopathology), as an emphysema indicator after 2 months in wildtypes, but only after 4 months in Trpa1-/- mice. Semiquantitative histopathological scores were not different between strains in either models. TRPA1 has a complex role in basal airway function regulation and inflammatory mechanisms. It protects against LPS-induced acute pneumonitis and hyperresponsiveness, but is required for CSE-evoked emphysema and respiratory deterioration. Further research is needed to determine TRPA1 as a potential pharmacological target in the lung.

Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial.

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium.Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB.Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ).Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P = 0.0002) scores were observed, with similar observations through 12 months.Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).

Elevated Circulating CD4+CD25+CD127-/low Regulatory T Cells in Patients with Non-asthmatic Eosinophilic Bronchitis.

PURPOSE: Non-asthmatic eosinophilic bronchitis (NAEB) is a common cause of chronic cough. It is characterized by sputum eosinophilia like asthma but lacks airway hyperresponsiveness. Regulatory T cells (Tregs) are recognized as immune suppressors and are involved in the pathogenesis of asthma. However, the relationship between Tregs and NAEB remains unknown. This study aimed to preliminarily explore the role of Tregs in NAEB by comparing circulating Tregs levels to asthma and healthy controls. METHODS: Fractional exhaled nitric oxide (FeNO), spirometry with bronchial provocation test, sputum induction and blood routine test were performed in all subjects. Peripheral blood mononuclear cells were used to detect the Tregs (CD4+CD25+CD127-/low) by flow cytometry. Relationship between the levels of circulating Tregs and clinical indexes was also observed. RESULTS: A total of 15 patients with NAEB, 20 patients with asthma and 11 healthy controls were included. The absolute numbers of circulating Tregs in the NAEB group (49.8 ± 18.9 × 103 cells/ml) and asthma group (53.3 ± 18.7 × 103 cells/ml) were higher than that in healthy control group (32.7 ± 11.6 × 103 cells/ml) (both P < 0.01). In total, the level of circulating Tregs showed positive correlation with FeNO (r = 0.30, P < 0.05). CONCLUSION: Tregs may play a key role not only in asthmatic patients, but also in patients with NAEB, as reflected by the elevated Tregs in peripheral blood.

The characteristics of the frequent exacerbator with chronic bronchitis phenotype and non-exacerbator phenotype in patients with chronic obstructive pulmonary disease: a meta-analysis and system review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients with different phenotypes show different clinical characteristics. Therefore, we conducted a meta-analysis to explore the clinical characteristics between the non-exacerbator (NE) phenotype and the frequent exacerbator with chronic bronchitis (FE-CB) phenotype among patients with COPD. METHODS: CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases were searched from the times of their inception to April 30, 2019. All studies that reported the clinical characteristics of the COPD phenotypes and which met the inclusion criteria were included. The quality assessment was analyzed by Cross-Sectional/Prevalence Study Quality recommendations. The meta-analysis was carried out using RevMan5.3. RESULTS: Ten cross-sectional observation studies (n = 8848) were included. Compared with the NE phenotype, patients with the FE-CB phenotype showed significantly lower forced expiratory volume in 1 s percent predicted (FEV1%pred) (mean difference (MD) -8.50, 95% CI -11.36--5.65, P < 0.001, I2 = 91%), forced vital capacity percent predicted (FVC%pred) [MD - 6.69, 95% confidence interval (CI) -7.73--5.65, P < 0.001, I2 = 5%], and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (MD -3.76, 95% CI -4.58--2.95,P < 0.001, I2 = 0%); in contrast, Charlson comorbidity index (MD 0.47, 95% CI 0.37-0.58, P < 0.001, I2 = 0], COPD assessment test (CAT) score (MD 5.61, 95% CI 4.62-6.60, P < 0.001, I2 = 80%), the quantity of cigarettes smoked (pack-years) (MD 3.09, 95% CI 1.60-4.58, P < 0.001, I2 = 41%), exacerbations in previous year (2.65, 95% CI 2.32-2.97, P < 0.001, I2 = 91%), modified Medical British Research Council (mMRC) score (MD 0.72, 95% CI 0.63-0.82, P < 0.001, I2 = 57%), and body mass index (BMI), obstruction, dyspnea, exacerbations (BODEx) (MD 1.78, 95% CI 1.28-2.28, P < 0.001, I2 = 91%), I2 = 34%) were significantly higher in patients with FE-CB phenotype. No significant between-group difference was observed with respect to BMI (MD-0.14, 95% CI -0.70-0.42, P = 0.62, I2 = 75%). CONCLUSION: COPD patients with the FE-CB phenotype had worse pulmonary function and higher CAT score, mMRC scores, frequency of acute exacerbations, and the quantity of cigarettes smoked (pack-years) than those with the NE phenotype.

Association of Nonobstructive Chronic Bronchitis With Respiratory Health Outcomes in Adults.

Importance: Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain. Objective: To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers. Design, Setting, and Participants: This prospective cohort study included 22 325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018. Exposures: Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years. Main Outcomes and Measures: Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis. Results: Among 22 325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11 082 ever smokers with 99 869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11 243 never smokers with 120 004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes. Conclusions and Relevance: The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies.

Comparison of signalment, clinical, laboratory and radiographic parameters in cats with feline asthma and chronic bronchitis.

OBJECTIVES: Feline asthma (FA) and feline chronic bronchitis (CB) are common respiratory conditions in cats, frequently referred to as 'feline lower airway disease'. However, the aetiologies of both inflammatory airway diseases are probably different. Little is known about the differences in signalment, clinical signs, laboratory abnormalities and radiographic features between cats with these two airway diseases. The aim of the study was to investigate whether certain parameters can help in differentiating between both diseases, as distinguished by airway cytology. METHODS: Seventy-three cats with FA and 24 cats with CB were included in the retrospective study. Inclusion criteria were compatible clinical signs and a cytological evaluation of bronchoalveolar lavage fluid indicating either FA (eosinophilic inflammation) or CB (neutrophilic inflammation) without cytological or microbiological evidence of bacterial infection. Parameters of signalment, physical examination, haematology and thoracic radiographs of both disease groups were compared statistically (P <0.05). RESULTS: The median age of cats with FA was 6 years, and was 7.5 years in cats with CB (P = 0.640). The most commonly reported clinical signs in both groups were a cough (95% FA/96% CB; P = 1.000), pathological pulmonary auscultatory sounds (82% FA/79% CB; P = 0.766) and dyspnoea (73% FA/79% CB; P = 0.601). Abnormal radiographic lung patterns were detected in 94% of cats with FA and 91% with CB (P = 0.629), respectively. Blood eosinophilia was significantly more common in cats with FA (40%) compared with CB (27%) (P = 0.026). CONCLUSIONS AND RELEVANCE: The study indicates that a differentiation of FA and CB by means of signalment, a single clinical sign, and haematological and radiographic findings is not possible.

Pulmonary Manifestations of Inflammatory Bowel Disease.

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.

Canine Chronic Bronchitis: An Update.

Chronic bronchitis is a syndrome defined by cough on most days for at least 2 months for which no specific cause can be identified. Older small breed dogs are most commonly affected, but bronchitis can also be documented in midsized and larger breed dogs. Diagnostic testing includes physical examination, laboratory testing, radiography, and airway evaluation via bronchoscopy, cytology, and culture. Treatment is directed at reducing exposure to irritants, reducing airway inflammation, and controlling cough.

Duration of treatment with inhaled corticosteroids in nonasthmatic eosinophilic bronchitis: a randomized open label trial.

BACKGROUND: Nonasthmatic eosinophilic bronchitis (NAEB) responds well to inhaled corticosteroids (ICS), while recurrence is common after discontinuing treatment. There are no data available to show whether treatment duration of ICS in patients with NAEB is related to recurrence. We aim to evaluate the effect of different duration of treatment with ICS on relapse of NAEB. METHODS: A total of 101 patients with NAEB were recruited to the open label, randomized, parallel-group trial. Patients were randomized to receive 1-month, 2-month, or 4-month treatment with inhaled budesonide (200 µg, twice daily). Sputum induction, cough visual analogue scale (VAS), and cough symptom score (CSS) were conducted at baseline and after completion of treatment. The patients were followed up for 1 year after treatment. The primary outcome was the relapse rate of NAEB in 1 year. RESULTS: ICS significantly decreased cough VAS, CSS, and sputum eosinophilia among these groups. There were no statistically significant between-group differences in cough VAS, CSS scores, and sputum eosinophil counts at the end of treatment, and no significant between-group differences in those changes from baseline to post-treatment. Significantly, more participants in the 1-month treatment group experienced a recurring episode of NAEB than those in the 3-month treatment group (41.9% versus 12.0%, p = 0.0137) at 1-year follow-up. The 2-month treatment group showed a lower tendency, with a relapse rate of 20.0% (p = 0.0644). CONCLUSIONS: Our results suggest that inhaled corticosteroids should be administrated for at least 2 months to reduce the relapse of NAEB. CLINICAL TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02002715). The reviews of this paper are available via the supplemental material section.

Clinical Features Of Women With COPD: Sex Differences In A Cross-Sectional Study In Spain ("The ESPIRAL-ES Study").

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 <5 (no impact), 5-9 (low), 10-20 (medium), >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.

The characteristics of the frequent exacerbators with chronic bronchitis phenotype and the asthma-chronic obstructive pulmonary disease overlap syndrome phenotype in chronic obstructive pulmonary disease patients: A meta-analysis and system review.

To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype.We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis.Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] -9.05, 95% confidence interval [CI] [-12.00, -6.10], P < .001, I = 66%), forced expiratory volume in 1 second (FEV1) (MD -407.18, 95% CI [-438.63, -375.72], P < .001, I = 33%), forced expiratory volume in 1 second percent predicted (MD -9.71, 95% CI [-12.79, -6.63], P < .001, I = 87%), FEV1/forced vital capacity (MD -5.4, 95% CI [-6.49, -4.30], P < .001, I = 0%), and body mass index (BMI) (MD -0.81, 95% CI [-1.18, -0.45], P < .001, I = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I = 86%) as compared to the ACO phenotype.Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx.This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.

Mucociliary Clearance in Former Tobacco Smokers with Both Chronic Obstructive Pulmonary Disease and Chronic Bronchitis and the Effect of Roflumilast.

Background: Little is known of the repeatability and reliability of mucociliary clearance (MCC) in former tobacco smokers who have both chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB). Less is known of the effect of roflumilast, a selective inhibitor of PDE4, on MCC in these patients. Methods: Former tobacco smokers with COPD and CB were treated for 4 weeks with either roflumilast, or placebo, in a randomized, crossover trial. The following were measured on two baseline and two posttreatment visits: MCC values through 90 minutes, following inhalation of 99mtechnetium sulfur colloid and gamma camera imaging; outer:inner (O:I) deposition ratio; forced expiratory volume in 1 second (FEV1); and symptom scores. Comparisons included: MCC measures through 30 minutes (MCC30), 60 minutes (MCC60), and 90 minutes (MCC90) on the two baseline visits (n = 9) and mean change [(roflumilast - baseline)-(placebo - baseline)] for MCC30, MCC60, MCC90, and FEV1 (n = 8). Associations between MCC measurements, FEV1 and O:I ratio with symptom scores were also examined. Results: Pearson correlation tests indicated good repeatability for baseline measures of MCC30, MCC60, and MCC90 and intraclass correlation coefficients indicated good reliability. Only FEV1 (percent predicted) improved significantly following roflumilast treatment. There were no statistically significant correlations between MCC measures and symptom scores. Lower FEV1 values were significantly associated with increased shortness of breath (dyspnea), and lower O:I ratios (more inner region deposition) were significantly associated with increased cough and sputum. Conclusions: Measurements of MCC30, MCC60, and MCC90 are repeatable and reliable in former tobacco smokers with both COPD and CB. One month of treatment with roflumilast did not improve MCC in this limited study. Airway narrowing in the larger, central airways of these subjects could lead to decreased FEV1, increased inner region deposition of the radiolabeled particles, and the associated increase in symptoms of dyspnea, cough, and sputum.

Clinical phenotypes of COPD and health-related quality of life: a cross-sectional study.

INTRODUCTION: The Spanish COPD guideline (GesEPOC) classifies COPD into four clinical phenotypes based on the exacerbation frequency and dominant clinical manifestations. In this study, we compared the disease-specific health-related quality of life (HRQoL) of patients with different clinical phenotypes. METHODS: This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018. Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire for COPD (SGRQ-c). RESULTS: Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS). The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes (P<0.001). Patients who were AE CB had significantly higher total CAT score than those with ACOS (P=0.033), AE NON-CB (P=0.001), and NON-AE (P<0.001). Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB (P=0.001) and NON-AE (P<0.001). However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS (P=0.187). There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them. CONCLUSION: Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components. Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components.