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1.
Respir Res ; 23(1): 52, 2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35255901

ABSTRACT

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.


Subject(s)
Body Mass Index , Bronchitis, Chronic/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Risk Assessment/methods , Surveys and Questionnaires , Aged , Bronchitis, Chronic/physiopathology , Comorbidity , Disease Progression , Female , Follow-Up Studies , Humans , Incidence , Male , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Severity of Illness Index
3.
Respir Med ; 181: 106385, 2021 05.
Article in English | MEDLINE | ID: mdl-33848923

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/epidemiology , Bronchitis, Chronic/mortality , Cardiovascular Diseases/complications , Adult , Bronchitis, Chronic/etiology , Bronchitis, Chronic/physiopathology , Cause of Death , Cohort Studies , Europe/epidemiology , Female , Follow-Up Studies , Forced Expiratory Volume , Forecasting , Humans , Male , Middle Aged , Multivariate Analysis , Prevalence , Smoking/adverse effects , Social Class , Time Factors , Vital Capacity
4.
Chest ; 160(3): 1026-1034, 2021 09.
Article in English | MEDLINE | ID: mdl-33839084

ABSTRACT

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.


Subject(s)
Asthma , Bronchitis, Chronic , Glucose/analysis , Metabolic Syndrome , Pulmonary Emphysema , Triglycerides/analysis , Adult , Asthma/diagnosis , Asthma/metabolism , Asthma/physiopathology , Biomarkers/analysis , Bronchitis, Chronic/diagnosis , Bronchitis, Chronic/metabolism , Bronchitis, Chronic/physiopathology , Correlation of Data , Female , Humans , Male , Metabolic Syndrome/blood , Metabolic Syndrome/diagnosis , Metabolic Syndrome/physiopathology , Nutrition Surveys/statistics & numerical data , Pulmonary Emphysema/diagnosis , Pulmonary Emphysema/metabolism , Pulmonary Emphysema/physiopathology , Respiratory Function Tests/methods , Symptom Assessment/methods , United States/epidemiology
5.
Am J Respir Cell Mol Biol ; 64(4): 441-452, 2021 04.
Article in English | MEDLINE | ID: mdl-33524306

ABSTRACT

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).


Subject(s)
Airway Remodeling/genetics , Bronchitis, Chronic/genetics , Gene Expression Profiling , Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/genetics , Regeneration/genetics , Transcriptome , Adult , Aged , Bronchitis, Chronic/pathology , Bronchitis, Chronic/physiopathology , Case-Control Studies , Disease Progression , Female , Humans , Longitudinal Studies , Lung/pathology , Male , Middle Aged , Pilot Projects , Prospective Studies , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Time Factors , Young Adult
6.
Thorax ; 76(4): 343-349, 2021 04.
Article in English | MEDLINE | ID: mdl-33408194

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/diagnostic imaging , Smokers , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Airway Remodeling , Bronchitis, Chronic/physiopathology , Female , Fractals , Humans , Male , Middle Aged , Quality of Life , Respiratory Function Tests , Risk Factors
7.
BMC Pulm Med ; 20(1): 254, 2020 Sep 29.
Article in English | MEDLINE | ID: mdl-32993591

ABSTRACT

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.


Subject(s)
Asthma/diagnosis , Bronchitis, Chronic/diagnosis , Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Emphysema/diagnosis , Quality of Life , Aged , Asthma/physiopathology , Asthma/psychology , Asthma/therapy , Bronchitis, Chronic/physiopathology , Bronchitis, Chronic/psychology , Bronchitis, Chronic/therapy , Cross-Sectional Studies , Disease Progression , Female , Health Status , Humans , Malaysia , Male , Middle Aged , Phenotype , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/psychology , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Emphysema/physiopathology , Pulmonary Emphysema/psychology , Pulmonary Emphysema/therapy , Severity of Illness Index , Surveys and Questionnaires
8.
Int J Mol Sci ; 21(11)2020 Jun 09.
Article in English | MEDLINE | ID: mdl-32526913

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/physiopathology , Cigarette Smoking/adverse effects , Pneumonia/physiopathology , TRPA1 Cation Channel/metabolism , Animals , Bronchitis, Chronic/chemically induced , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Female , Lipopolysaccharides/toxicity , Lung/metabolism , Lung/pathology , Male , Mice, Inbred C57BL , Mice, Mutant Strains , Peroxidase/metabolism , Plethysmography, Whole Body , Pneumonia/chemically induced , Pulmonary Emphysema/chemically induced , Pulmonary Emphysema/metabolism , Pulmonary Emphysema/pathology , Respiratory Function Tests , TRPA1 Cation Channel/genetics
9.
Lung ; 198(3): 491-497, 2020 06.
Article in English | MEDLINE | ID: mdl-32367413

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/immunology , CD4 Antigens/metabolism , Eosinophilia/immunology , Immunity, Cellular , Interleukin-2 Receptor alpha Subunit/metabolism , Interleukin-7 Receptor alpha Subunit/metabolism , T-Lymphocytes, Regulatory/immunology , Adult , Bronchitis, Chronic/diagnosis , Bronchitis, Chronic/physiopathology , Eosinophilia/pathology , Exhalation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Spirometry , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathology
10.
Am J Respir Crit Care Med ; 202(5): 681-689, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32407638

ABSTRACT

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).


Subject(s)
Ablation Techniques/methods , Bronchi/surgery , Bronchitis, Chronic/surgery , Aged , Bronchitis, Chronic/physiopathology , Disease Progression , Female , Follow-Up Studies , Forced Expiratory Volume , Humans , Male , Prospective Studies , Quality of Life , Time Factors , Treatment Outcome
11.
BMC Pulm Med ; 20(1): 103, 2020 Apr 23.
Article in English | MEDLINE | ID: mdl-32326924

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Asthma/epidemiology , Asthma/physiopathology , Body Mass Index , Bronchitis, Chronic/epidemiology , Disease Progression , Dyspnea/epidemiology , Humans , Observational Studies as Topic , Phenotype , Pulmonary Disease, Chronic Obstructive/epidemiology , Quality of Life , Respiratory Function Tests
12.
JAMA Intern Med ; 180(5): 676-686, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32119036

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/physiopathology , Lung/physiopathology , Smoking/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Asthma/physiopathology , Female , Humans , Male , Middle Aged , Prospective Studies , Respiratory Function Tests , Smokers , Young Adult
13.
Am J Med ; 133(1): 39-43, 2020 01.
Article in English | MEDLINE | ID: mdl-31398306

ABSTRACT

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.


Subject(s)
Inflammatory Bowel Diseases/complications , Lung Diseases/etiology , Bronchiectasis/etiology , Bronchiectasis/physiopathology , Bronchiolitis/etiology , Bronchiolitis/physiopathology , Bronchitis, Chronic/etiology , Bronchitis, Chronic/physiopathology , Humans , Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/physiopathology , Lung Diseases/physiopathology , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/physiopathology , Pleurisy/etiology , Pleurisy/physiopathology , Pulmonary Eosinophilia/etiology , Pulmonary Eosinophilia/physiopathology , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/physiopathology , Tracheitis/etiology , Tracheitis/physiopathology , Tumor Necrosis Factor Inhibitors/adverse effects
14.
J Feline Med Surg ; 22(7): 649-655, 2020 07.
Article in English | MEDLINE | ID: mdl-31483195

ABSTRACT

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.


Subject(s)
Asthma , Bronchitis, Chronic , Cat Diseases , Animals , Asthma/diagnosis , Asthma/physiopathology , Asthma/veterinary , Bronchitis, Chronic/diagnosis , Bronchitis, Chronic/physiopathology , Bronchitis, Chronic/veterinary , Cat Diseases/diagnosis , Cat Diseases/physiopathology , Cats , Diagnosis, Differential
15.
Vet Clin North Am Small Anim Pract ; 50(2): 393-404, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31812219

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/veterinary , Dog Diseases , Animals , Bronchitis, Chronic/diagnosis , Bronchitis, Chronic/physiopathology , Bronchitis, Chronic/therapy , Dog Diseases/diagnosis , Dog Diseases/physiopathology , Dog Diseases/therapy , Dogs , Prognosis
16.
Int J Chron Obstruct Pulmon Dis ; 14: 2469-2478, 2019.
Article in English | MEDLINE | ID: mdl-31806956

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/physiopathology , Health Status Disparities , Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Emphysema/physiopathology , Aged , Bronchitis, Chronic/diagnosis , Bronchitis, Chronic/epidemiology , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Emphysema/diagnosis , Pulmonary Emphysema/epidemiology , Quality of Life , Risk Factors , Sex Factors , Smokers , Smoking/adverse effects , Smoking/epidemiology , Spain/epidemiology
17.
Ther Adv Respir Dis ; 13: 1753466619891520, 2019.
Article in English | MEDLINE | ID: mdl-31847717

ABSTRACT

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.


Subject(s)
Bronchitis, Chronic/drug therapy , Budesonide/administration & dosage , Eosinophilia/drug therapy , Glucocorticoids/administration & dosage , Administration, Inhalation , Adult , Bronchitis, Chronic/physiopathology , Cough/drug therapy , Cough/etiology , Duration of Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Sputum , Young Adult
18.
Medicine (Baltimore) ; 98(46): e17996, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31725666

ABSTRACT

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.


Subject(s)
Lung Diseases, Obstructive/epidemiology , Lung Diseases, Obstructive/physiopathology , Asthma/epidemiology , Asthma/physiopathology , Body Mass Index , Bronchitis, Chronic/epidemiology , Bronchitis, Chronic/physiopathology , Cigarette Smoking/epidemiology , Disease Progression , Dyspnea/epidemiology , Humans , Observational Studies as Topic , Phenotype , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of Life , Respiratory Function Tests
19.
J Aerosol Med Pulm Drug Deliv ; 32(4): 189-199, 2019 08.
Article in English | MEDLINE | ID: mdl-30964381

ABSTRACT

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.


Subject(s)
Aminopyridines/administration & dosage , Benzamides/administration & dosage , Bronchitis, Chronic/drug therapy , Phosphodiesterase 4 Inhibitors/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Aged , Aminopyridines/pharmacology , Benzamides/pharmacology , Bronchitis, Chronic/physiopathology , Cross-Over Studies , Cyclopropanes/administration & dosage , Cyclopropanes/pharmacology , Double-Blind Method , Female , Forced Expiratory Volume , Humans , Male , Mucociliary Clearance/drug effects , Phosphodiesterase 4 Inhibitors/pharmacology , Pulmonary Disease, Chronic Obstructive/physiopathology , Reproducibility of Results , Tobacco Smoking/physiopathology
20.
J Aerosol Med Pulm Drug Deliv ; 32(4): 175-188, 2019 08.
Article in English | MEDLINE | ID: mdl-30848685

ABSTRACT

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study compared the use of change in penetration index (PI) with conventional whole lung clearance in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (1) healthy nonsmoking controls (n = 9), (2) smoking controls who were current smokers with normal lung function (n = 10), and (3) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volume at 1 second (FEV1) for the three groups was 109 (±18), 94 (±5), and 78 (±12), respectively. Following inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Total lung clearance and tracheobronchial clearance (TBC; normalized to 24-hour clearance) were calculated. A novel parameter, the normalized change in PI (NOCHIP), was also evaluated. PI is the ratio of counts between outer and inner lung zones normalized to lung volume. Results: More aerosol was deposited in central airways in COPD compared to nonsmoking controls, using 24-hour clearance measurements (p < 0.001). Smoking controls had intermediate values. The optimal endpoint for MCC assessment was chosen to be 3 hours, when intersubject variability was minimal, while preserving a measure of early clearance. There was no statistical difference between the three groups in mean total lung clearance, or TBC, at 3 hours. NOCHIP at 3 hours was reduced significantly, compared to nonsmoking controls, in both smoking controls (p = 0.007) and COPD (p < 0.0001). It also correlated with FEV1 (p = 0.003). A higher proportion of smoking control subjects had NOCHIP values in the nonsmoking control range than in the COPD group. Conclusions: NOCHIP was a more sensitive measure of MCC than whole lung clearance and TBC in mild-to-moderate COPD.


Subject(s)
Bronchitis, Chronic/physiopathology , Mucociliary Clearance/physiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Smoking/physiopathology , Aerosols/administration & dosage , Aged , Case-Control Studies , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Radionuclide Imaging , Severity of Illness Index , Technetium/administration & dosage
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