Early-stage Chronic Obstructive Pulmonary Disease Research Articles

International research progress of risk factors, diagnosis and management in early chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) has a high global morbidity and mortality and a severe disease burden, yet progress in treatment and prevention has been slow in recent decades. Early COPD has few symptoms and is severely underdiagnosed and undertreated; it is crucial to search for effective clues of early COPD and provide management interventions. By reviewing the definition, risk factors, diagnosis and management interventions, this study explores the disease evolution of early-stage COPD, which can help clinical practice to develop more effective preventive and therapeutic strategies for stopping or slowing down the natural progression of the disease, improving the long-term prognosis, and reducing the disease burden.

Cardiovascular Prognosis of Subclinical Chronic Obstructive Pulmonary Disease in Patients with Suspected or Confirmed Coronary Artery Disease.

Chronic obstructive pulmonary disease (COPD) worsens prognosis in patients with coronary artery disease (CAD). However, the cardiovascular prognosis in patients with stable or mildly symptomatic COPD remains unclear. Here, we sought to determine the long-term cardiovascular events in patients with subclinical or early-stage COPD with concomitant CAD. This was a longitudinal analytical study involving 117 patients with suspected or established CAD who underwent assessment of pulmonary function by spirometry and who were followed up for six years (March 2015-January 2021). The patients were divided into two groups, one comprising COPD (n=44) and the other non-COPD (n=73) patients. Cox regression was used to evaluate the association between COPD and cardiovascular events, with adjustment for the established CAD risk factors, and the effect size was measured by the Cohen test. COPD patients were older (p=0.028), had a greater frequency of diabetes (p=0.026), were more likely to be smokers (p<0.001), and had higher modified Medical Research Council scores (p<0.001). There was no difference between the groups regarding gender, body mass index, hypertension, dyslipidemia, family history of CAD, and type of angina. CAD frequency and the proportion of patients with severe and multivessel CAD were significantly higher among COPD than among non-COPD patients (all p<0.001). At six-year follow-up, patients with COPD were more likely to have experienced adverse cardiovascular events than those without COPD (p<0.001; effect size, 0.720). After adjusting for established CAD risk factors, COPD occurrence remained an independent predictor for long-term adverse cardiovascular events (OR: 5.13; 95% CI: 2.29-11.50; p<0.0001). COPD was associated with increased severity of coronary lesions and a greater number of adverse cardiovascular events in patients with suspected or confirmed CAD. COPD remained a predictor of long-term cardiovascular events in stable patients with subclinical or early-stage of COPD, independently of the established CAD risk factors.

Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease

Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.

Phase-contrast virtual chest radiography

Respiratory X-ray imaging enhanced by phase contrast has shown improved airway visualization in animal models. Limitations in current X-ray technology have nevertheless hindered clinical translation, leaving the potential clinical impact an open question. Here, we explore phase-contrast chest radiography in a realistic in silico framework. Specifically, we use preprocessed virtual patients to generate in silico chest radiographs by Fresnel-diffraction simulations of X-ray wave propagation. Following a reader study conducted with clinical radiologists, we predict that phase-contrast edge enhancement will have a negligible impact on improving solitary pulmonary nodule detection (6 to 20 mm). However, edge enhancement of bronchial walls visualizes small airways (< 2 mm), which are invisible in conventional radiography. Our results show that phase-contrast chest radiography could play a future role in observing small-airway obstruction (e.g., relevant for asthma or early-stage chronic obstructive pulmonary disease), which cannot be directly visualized using current clinical methods, thereby motivating the experimental development needed for clinical translation. Finally, we discuss quantitative requirements on distances and X-ray source/detector specifications for clinical implementation of phase-contrast chest radiography.

Experimental feasibility of xenon-enhanced dual-energy radiography for imaging of lung function

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. We experimentally investigated the feasibility of two-dimensional xenon-enhanced dual-energy (XeDE) radiography for imaging of lung function. We optimized image quality under quantum-noise-limited conditions using a chest phantom consisting of a rectangular chamber representing the thoracic volume and PMMA slabs simulating x-ray attenuation by soft tissue. A sealed, air-filled cavity with thin PMMA walls was positioned inside the chamber to simulate a 2 cm thick ventilation defect. The chamber was ventilated with xenon and dual-energy imaging was performed using a diagnostic x-ray tube and a flat-panel detector. The contrast-to-noise ratio of ventilation defects normalized by patient x-ray exposure maximized at a kV-pair of approximately 60/140-kV and when approximately one third of the total exposure was allocated to the HE image. We used the optimized technique to image a second phantom that contained lung-parenchyma-mimicking PMMA clutter, rib-mimicking aluminum slats and an insert that simulated ventilation defects with thicknesses ranging from 0.5 cm to 2 cm and diameters ranging from 1 cm to 2 cm. From the resulting images we computed the area under the receiver operating characteristic curve (AUC) of the non-prewhitening model observer with an eye filter and internal noise. For a xenon concentration of 75%, good AUCs (i.e. 0.8–0.9) to excellent AUCs (i.e. >0.9) were obtained when the defect diameter is greater than 1.3 cm and defect thickness is 1 cm. When the xenon concentration was reduced to 50%, the AUC was ∼0.9 for defects 1.2 cm in diameter and ∼1.5 cm in thickness. Two-dimensional XeDE radiography may therefore enable detection of functional abnormalities associated with early-stage COPD, for which xenon ventilation defects can occupy up to 20% of the lung volume, and should be further developed as a low-cost alternative to MRI-based approaches and a low-dose alternative to CT-based approaches.

Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation.

Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-β1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.

Control of chronic obstructive pulmonary disease in urban populations: findings from a cross-sectional prevalence survey in Shenzhen, China.

The prevalence of chronic obstructive pulmonary disease (COPD) among urban populations is generally lower than rural residents, but the disease burden is still high. We conducted a cross-sectional prevalence survey of COPD among residents aged ≥40 years in an emerging city Shenzhen, China from September 2018 to June 2019. Through multi-stage stratified random sampling, a total of 4157 eligible participants were invited to complete a questionnaire and to take the spirometry test; 3591 with available data were enrolled in the final analysis. Individuals were diagnosed with COPD if the post-bronchodilator FEV1/FVC ratio was less than 0.7. The estimated standardized prevalence of COPD among residents over 40 years old in Shenzhen was 5.92% (95% confidential intervals[CI] 4.05-8.34). Risk factors for COPD included elder age (adjusted odds ratio 1.206, 95% CI 1.120-1.299 per 10-year increase), smoking over 20 pack-years (1.968, 1.367-2.832), history of chronic bronchitis (1.733, 1.036-2.900) or asthma (4.920, 2.425-9.982), and exposure to higher annual minimum concentrations of ambient SO2 (1.156, 1.053-1.270 per 1-μg/m3 increase). Among 280 spirometry-diagnosed patients, most (221, 78.93%) patients were classified as mild COPD (GOLD stage I). This survey found thatthe prevalence of COPD in Shenzhenis low and most patients had mild symptoms, thus recommended screening using spirometry in primary health care to detect early-stage COPD. Increased risk from the exposure to air pollutants also indicated the urgent need for environmental improvement in city settings.

Diagnostic sensitivity of impulse oscillometry in early detection of patients exposed to risk factors chronic obstructive pulmonary diseases.

Background: Impulse oscillometry (IOS) is a method that does not depend on the cooperation of the patient and can detect small airway diseases with higher sensitivity than spirometry. However, the clinical application value of IOS in the screening of patients exposed to risk factors COPD and early diagnosis remains unclear. The aim of this study is to evaluate diagnostic sensitivity of IOS in the early detection of patients exposed to risk factors COPD. Methods: A prospective cross-sectional study was conducted in Rasoul Akram Hospital, Tehran, Iran, from 2013 to 2015. 28 patients with COPD risk factors and normal spirometry participated in the study. The IOS was performed. We obtained the respiratory resistance and impedance of 5 Hz (R5) and 20 Hz (R20) and 5 Hz (Z5), respectively. The data were analyzed using SPSS version 17 using Chi-square and two independent sample t-test. Spearman correlation test was used to measure the correlation of oscillometry parameters in the diagnosis of COPD. P-value <0.05 was considered significantfor all statistical analyses. Results: The mean patient age was 55.50±11.27 years. In this study, the sensitivity of Z5, R5, and R20 was respectively 28.5%, 25%, and 31.5%. All oscillometry parameters were significantly correlated with each other but none of the oscillometry parameters showed significant correlations with FEV1/FVC (rZ5=0.018, rR5=0.082, rR20=0.041 and PZ5=0.932, PR5=0.711, P R20=0.850). According to the results, only 9 patients (32.5%) with normal values of FEV1/FVC had abnormal values of oscillometry. Conclusion: IOS has a low sensitivity and cannot be used in the screening of early-stage chronic obstructive pulmonary disease.

High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I\u2013II): study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China

IntroductionThe presence of increased oxidative stress and airway inflammation has been proven in subjects with chronic obstructive pulmonary disease (COPD). Several studies have demonstrated that drugs with antioxidant and anti-inflammatory properties such as N-acetylcysteine (NAC) can reduce the rate of exacerbations in patients with COPD. However, the beneficial effects of NAC in early-stage COPD are minimally discussed. We are investigating whether high-dose NAC has therapeutic effects in Chinese patients with early-stage COPD.Method and analysisA randomized, double-blinded, placebo-controlled, parallel-group, multicenter clinical trial is evaluating the efficacy and safety of NAC for the long-term treatment of patients with early-stage COPD at 24 centers in China. Subjects aged 40–80 years and recruited by physicians or researchers with special training will be randomized to either NAC 600 mg twice daily group or matching placebo group for 2 years. Measurements will include forced expiratory volume in 1 s (FEV1), the number of COPD exacerbations, health-related quality, and pharmacoeconomic analysis.DiscussionCurrently, there are no randomized controlled trials with high-dose N-acetylcysteine (600 mg twice daily) for patients with mild-to-moderate COPD (GOLD I–II). We designed this multicenter randomized controlled trial (RCT) to assess the effectiveness, safety, and cost-effectiveness of long-term treatment with high-dose N-acetylcysteine. The results of this trial may guide clinical practice and change the standard of early COPD management.Trial registrationChinese Clinical Trial Registry ChiCTR-IIR-17012604. Registered on 07 September 2017.

Treatment modality and outcomes among early-stage non-small cell lung cancer patients with COPD: a cohort study.

BackgroundWhile there is an increasing number of early-stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), there are no specific clinical guidelines for treating them. This study aims to evaluate different treatment modalities and corresponding clinical outcomes among early-stage NSCLC patients with COPD.MethodsWe retrospectively reviewed 692 patients with stage I and II NSCLC and COPD from January 2012 to June 2014. Patients were categorized into four groups according to primary treatment modality: surgery only group (n=442), surgery with adjuvant treatment group (n=157), radiotherapy (RT) group (n=48), and supportive care (SC)-only group (n=45).ResultsOverall, mortality rate was the highest in the SC-only group (35.7 deaths per 100 person-years), followed by RT group (21.5 deaths per 100 person-years), surgery with adjuvant treatment group (8.9 deaths per 100 person-years) and surgery only group (7.2 deaths per 100 person-years). The adjusted hazard ratios (HR) for all-cause mortality compared to the surgery only group were 1.18 (95% CI, 0.84–1.67) in surgery with adjuvant treatment group, 1.61 (95% CI, 1.01–2.57) in RT group and 3.23 (95% CI, 1.99–5.23) in SC-only group.ConclusionsSurgical resection should be considered as the first choice for early-stage NSCLC with COPD. Despite poor lung function or general patient condition, RT rather than SC can be an alternative option if surgery is not feasible. A multi-disciplinary approach and active communication between patients and physicians might be helpful for adequate decision-making regarding treatment for patients with early-stage NSCLC and COPD.

Morphological overview of cardiovascular comorbidities in chronic obstructive pulmonary disease: Frank's sign

ObjectiveCardiovascular diseases are the most common and important comorbidities in patients with chronic obstructive pulmonary disease (COPD). Literature indicates that there may be a relationship between diagonal earlobe crease (DELC) and coronary artery disease (CAD). Accordingly, the present study aimed to assess the relationship with DELC and cardiac comorbidities in patients with COPD during routine physical examination. Materials and MethodsIn this prospective cohort study, we evaluated the demographic data, pulmonary function test (PFT) results, lipid profile, oxygen saturation, and the presence of DELC in patients with COPD and control subjects. ResultsDELC was diagnosed in 155 (62%) of COPD patients and these patients had a higher prevalence of CAD (p = 0.044). Moreover, DELC was diagnosed in 135 men (68.5%) and 20 (37.7%) women in the COPD group (p<0.001) and in 39 (48.8%) men and 14 (56.0%) women in the control group (p = 0.527). On the other hand, CAD was diagnosed in 18% of patients with early-stage COPD (n = 104) and in 30.8% of patients with late-stage COPD (n = 146) (p = 0.041). The sensitivity and specificity of DELC positivity in predicting CAD were 80.65% and 44.15% in COPD patients, respectively. ConclusionThe presence of cardiac comorbidities in COPD patients may play a vital role in the severity of the disease, exacerbations, and may also reduce the treatment response. Accordingly, an earlobe examination of patients with COPD may be useful in predicting the presence of cardiac comorbidities with high sensitivity.

Analyze and Identify Peiminine Target EGFR Improve Lung Function and Alleviate Pulmonary Fibrosis to Prevent Exacerbation of Chronic Obstructive Pulmonary Disease by Phosphoproteomics Analysis

Chronic obstructive pulmonary disease (COPD) has been a major public health problem and is still a formidable challenge for clinicians. It is urgent to find new compounds for minimizing the risk of disease progression and exacerbation especially in the early phase of COPD. A traditional Chinese medicine (TCM) formula, Chuan Bei Pi Pa dropping pills (CBPP), was tested in this study to investigate its potential mechanisms in preventing the exacerbation of COPD. Phosphoproteomics analysis for a smog stimulated early stage COPD mice model was employed to detect the underlying molecular mechanisms of CBPP. In addition, protein–protein interaction (PPI) and bioinformatics analyses were included to analyze the key proteins and predict the key bioactive compounds. The results indicated that peiminine (PEI) target epidermal growth factor receptor (EGFR) prevented the exacerbation of COPD by inhibiting the EGFR signaling pathway, and ursolic acid (UA) can alleviate inflammation disorders via inhibition of CASP3 on mitogen-activated protein kinase (MAPK) signaling pathway. After in vivo and in vitro evaluations, we revealed that PEI from CBPP, as a lead compound, can improve lung function and alleviate pulmonary fibrosis by acting on the EGFR and MLC2 signaling pathways. Furthermore, the approach described here is an effective way to analyze and identify the bioactive ingredients from a mixture by functional proteomics analysis.

Tiotropium discontinuation in patients with early-stage COPD: a prospective observational cohort study.

BackgroundTiotropium improves lung function and ameliorates the annual decline in forced expiratory volume in 1 s (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown.MethodsIn this prospective cohort observational follow-up study, patients who had completed the Tiotropium in Early-Stage COPD (Tie-COPD) trial were followed for a maximum of 3 years, continuing or discontinuing treatment according to their willingness. The outcomes measured were spirometry parameters, COPD exacerbations, COPD Assessment Test (CAT) scores, Clinical COPD Questionnaire (CCQ) scores, modified Medical Research Council (mMRC) scores and the use of respiratory medications.ResultsOut of 376 patients, 262 (126 in the post-placebo group and 136 in the post-tiotropium group) completed the maximum 3-year follow-up after the study medication was withdrawn. After discontinuation, the decrease in FEV1 and forced vital capacity (FVC) did not differ significantly between the two groups, and neither did their annual decline. In addition, the frequency of acute COPD exacerbations and the mMRC scores were similar between the two groups after medication withdrawal. Both the mean CAT and CCQ scores were significantly lower in the post-tiotropium group than in the post-placebo group (p<0.05 for all comparisons) at the 1-year follow-up after withdrawal, but they were not different at the next follow-up.ConclusionWithdrawal of tiotropium treatment in early-stage COPD resulted in difference reduction of both FEV1 and FVC, indicating that treatment should be continued.

Tiotropium Withdrawal in Early-Stage Chronic Obstructive Pulmonary Disease

Background: Tiotropium improves lung function and ameliorates the annual decline in the forced expiratory volume in 1 second (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown. Methods: In this prospective cohort observational follow-up study, patients who had completed the tiotropium in early-stage COPD (Tie-COPD) trial were followed for a maximum of 3 years, continuing or discontinuing treatment according to their willingness. The outcomes measured were spirometry parameters, COPD exacerbations, COPD Assessment Test (CAT) scores, Clinical COPD Questionnaire (CCQ) scores, modified British Medical Research Council (mMRC) scores and the use of respiratory medications. Results: Of 353 patients, 262 (126 in post-placebo group and 136 in post-tiotropium group) completed the maximum 3-year follow-up after the study medication was withdrawn. After discontinuation, both the FEV1 and forced vital capacity decreased, with no significant difference between the two groups. The frequency of acute COPD exacerbations and the mMRC scores were also similar between the two groups after medication withdrawal. Both the mean CAT and CCQ scores were significantly lower in the post-tiotropium group than in the post-placebo group (P<0.05 for all comparisons) at the 1-year follow-up after withdrawal, but they were not different at the next follow-up. Conclusion: Tiotropium should be continued because the lung function of the patients who had received regular treatment with tiotropium began to decline after tiotropium was withdrawn. Funding: Supported by grants from the National Key Technology Research and Development Program of the 12th and 13th National 5-Year Development Plan (2012BAI05B01 and 2016YFC1304100). Declaration of Interest: No potential conflict of interest relevant to this article was reported. Ethical Approval: The trial protocol was approved by the local institutional review board or independent ethics committee at each site according to the requirement of the Chinese guidelines for Good Clinical Practice. All participants provided written informed consent before enrollment.

A Novel Murine Chronic Obstructive Pulmonary Disease Model and the Pathogenic Role of MicroRNA-21

Chronic obstructive pulmonary disease (COPD) is a multi-pathogenesis chronic lung disease. The mechanisms underlying COPD have not been adequately illustrated. Many reseachers argue that microRNAs (miRs) could play a crucial role in COPD. The classic animal model of COPD is both time consuming and costly. This study proposes a novel mice COPD model and explores the role of miR-21 in COPD. A total of 50 wide-type (WT) C57BL/6 mice were separated into five euqlly-sized groups—(1) control group (CG), (2) the novel combined method group (NCM, cigarette smoke (CS) exposure for 28 days combined with cigarette smoke extract (CSE) intraperitoneal injection), (3) the short-term CS exposure group (SCSE, CS exposure for 28 days), (4) the CSE intraperitoneal injection group (CSEII, 28 days CSE intraperitoneal injection), and (5) the long-term CS exposure group (LCSE, CS exposure).The body weight gain of mice were recorded and lung function tested once the modeling was done. The pathological changes and the inflammation level by hematoxylin eosin (H&E) staining and immunohistochemical staining (IHS) on the lung tissue sections were also evaluated. The level of miR-21 in the mice lungs of the mice across all groups was detected by RT-qPCR and the effects of miR-21 knock-down in modeled mice were observed. The mice in LCSE and NCM exhibited the most severe inflammation levels and pathological and pathophysiological changes; while the changes for the mice in SCSE and CSEII were less, they remained more severe than the mice in the CG. The level of miR-21 was found to be negatively correlated with lung functions. Moreover, knocking miR-21 down from the modeled mice, ameliorated all those tested COPD-related changes. Our novel modeling method detected virtually the same changes as those detected in the classic method in WT mice, but in less time and cost. Further, it was determined that the level of miR-21 in the lungs could be an indicator of COPD severity and blocking functions of miR-21 could be a potential treatment for early stage COPD.

Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype

BackgroundSmoking is the main risk factor for chronic obstructive pulmonary disease (COPD). Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function. Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown. The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference.MethodWe employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18). Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest.ResultsMore pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress. Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT < −950 Hounsfield Units (HU), and regulation of actin cytoskeleton correlated with FEV1 and FEV1/FVC in female COPD patients. Alterations observed in the corresponding male cohort were minor.ConclusionThe identified molecular pathways suggest dysregulation of several phagocytosis-related pathways in BAL cells in female COPD patients, with correlation to both the level of obstruction (FEV1/FVC) and disease severity (FEV1) as well as emphysema (CT < −950 HU) in women.Trial registrationNo.: NCT02627872, retrospectively registered on December 9, 2015.

The Administration of Tiotropium in Patients With Early-stage Chronic Obstructive Pulmonary Disease Resulted in Improved Pulmonary Function at 2 Years

Rashid Riaz, MD, Leah Lande, MD, and Dana Zappetti, MD Synopsis: In this 2-year, multicenter, randomized, double-blind, placebo-controlled trial, the use of tiotropium in patients with chronic obstructive pulmonary disease Global Initiative for Chronic Obstructive Lung Disease stage 1 and stage 2 disease resulted in improved forced expiratory volume in 1 second throughout the trial duration, reduced rate of decline in forced expiratory volume in 1 second after bronchodilator use over 24 months, decreased frequency of exacerbations, and improved quality of life assessments compared with placebo. However, it remains unclear whether the use of tiotropium alters the long-term disease course in patients with chronic obstructive pulmonary disease. Source: Yumin Zhou, Nan-shan Zhong, Xiaochen Li, et al. Tiotropium in early-stage chronic obstructive pulmonary disease. N Engl J Med 2017;377:923–935.

Small airway disease: A different phenotype of early stage COPD associated with biomass smoke exposure.

Chronic exposure to biomass smoke (BS) can significantly compromise pulmonary function and lead to chronic obstructive pulmonary disease (COPD). To determine whether BS exposure induces a unique phenotype of COPD from an early stage, with different physiopathological features compared with COPD associated with smoking (cigarette-smoke (CS) COPD), we assessed the physiopathology of early COPD associated with BS exposure (BS COPD) by incorporating spirometry, high-resolution computed tomography (HRCT) imaging, bronchoscopy and pathological examinations. In this cross-sectional study, we recruited 29 patients with BS COPD, 31 patients with CS COPD and 22 healthy controls, including 12 BS-exposed subjects who did not smoke and 10 healthy smokers without BS exposure. Spirometry, HRCT scans, bronchoscopy and bronchial mucosa biopsies were performed to assess lung function, emphysema and air trapping, as well as the pathological characteristics and levels of inflammatory cells in bronchoalveolar lavage fluid (BALF). Among COPD patients with mild-to-moderate airflow limitation, BS exposure caused greater small airway dysfunction in BS COPD patients, although these patients had less emphysema and air trapping, as detected by HRCT (P < 0.05). We also observed significantly thicker basement membranes and greater endobronchial pigmentation in BS COPD than in CS COPD (P < 0.05). Moreover, patients with BS COPD exhibited greater macrophage and lymphocyte infiltration but reduced neutrophil infiltration in their BALF (P < 0.05). We used both radiology and pathology to document a distinct COPD phenotype associated with BS exposure. This is characterized by small airway disease.

Respiratory constraints during activities in daily life and the impact on health status in patients with early-stage COPD: a cross-sectional study.

In patients with chronic obstructive pulmonary disease (COPD), exercise capacity is reduced, resulting over time in physical inactivity and worsened health status. It is unknown whether ventilatory constraints occur during activities of daily life (ADL) in early stages of COPD. The aim of this study was to assess respiratory mechanics during ADL and to study its consequences on dyspnoea, physical activity and health status in early-stage COPD compared with healthy controls. In this cross-sectional study, 39 early-stage COPD patients (mean FEV1 88±s.d. 12% predicted) and 20 controls performed 3 ADL: climbing stairs, vacuum cleaning and displacing groceries in a cupboard. Respiratory mechanics were measured during ADL. Physical activity was measured with accelerometry. Health status was assessed by the Nijmegen Clinical Screening Instrument. Compared with controls, COPD patients had greater ventilatory inefficiency and higher ventilatory requirements during ADL (P<0.05). Dyspnoea scores were increased in COPD compared with controls (P<0.001). During ADL, >50% of the patients developed dynamic hyperinflation in contrast to 10–35% of the controls. Higher dyspnoea was scored by patients with dynamic hyperinflation. Physical activity was low but comparable between both groups. From the patients, 55–84% experienced mild-to-severe problems in health status compared with 5–25% of the controls. Significant ventilatory constraints already occur in early-stage COPD patients during common ADL and result in increased dyspnoea. Physical activity level is not yet reduced, but many patients already experience limitations in health status. These findings reinforce the importance of early diagnosis of COPD and assessment of more than just spirometry.

Symptoms and quality of life in patients with chronic obstructive pulmonary disease: are there patient_defined outcomes or predictive factors?

Novel medications for therapy of chronic obstructive pulmonary disease (COPD), primarily long-acting bronchodilators, could reduce severity of symptoms. Nevertheless, 50% to 70% of patients continue to experience significant dyspnea despite the therapy. Early diagnosis of COPD is a quite difficult clinical problem, whereas an active treatment is usually required at early-stage disease because of decreasing physical tolerance and, importantly, rapidly declining pulmonary function. Novel fixed combinations of long-acting beta-2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) deliver both the drugs in a single inhaler. These combinations have been shown to be more effective compared to monotherapy with the components. One of new LABA/LAMA combinations is tiotropium/olodaterol combination (Spiolto Respimat). Several large clinical trials (TONADO 1 and 2, ОTEMTO 1 and 2) demonstrated significant improvement in quality of life and dyspnea in patients with COPD taking the tiotropium/olodaterol combination. This combined drug was highly effective in early-stage COPD.