Chronic obstructive pulmonary disease in China: a nationwide prevalence study

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder with varying presentations and progression, but limited disease-modifying therapies. Trajectories of lung function decline in COPD differ significantly between individuals, with differences detectable in young adulthood. "Early disease" (initial manifestations in young individuals) should be distinguished from "late mild disease" (disease of mild severity in older individuals potentially present for decades). For research purposes, we propose an operational definition of early COPD: ever-smokers (≥10 pack-years) younger than 50 years with any of these abnormalities: (1) FEV1/FVC< lower limit of normal; (2) compatible CT abnormalities (airway abnormality and/or emphysema); or (3) FEV1 decline (≥60 mL/year). Biological underpinnings of early COPD are quite complex. Recent evidence implies that cigarette smoke-exposure induces sequential, stereotypical changes in distal airways, initially without inflammatory cell infiltration. Epithelial reprogramming is associated with mucus that is less readily cleared and with polymeric immunoglobulin receptor down-regulation accompanied by focal airway injury. Resulting differences in the community structure of the lung microbiome may be mechanistically important. Global gene analysis suggests that tissue degradation around small airways predominates over repair. Emphysema might also develop in early COPD due to loss of pulmonary endothelial cell-derived factors. To reduce COPD's long-term societal impact, the goal of interventions must change, from solely focusing on reducing symptoms and exacerbations in advanced disease, to halting pathological progression in early disease. This review attempts to stimulate studies investigating younger smokers to understand the causes, progression, clinical expression and potential therapeutic targets of early COPD.

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At the Root: Defining and Halting Progression of Early Chronic Obstructive Pulmonary Disease.

Objectives Increasingly, there is emphasis on identifying and initiating treatment of osteoarthritis (OA) in the early phases of the disease. This study aimed to identify the perceived barriers and facilitators to managing clients with early knee OA and the contextual factors affecting implementation of care by physical therapists (PTs). Design Qualitative study using in-depth semistructured interviews with 33 PTs. The interviews were audio-recorded, transcribed verbatim and analysed inductively using thematic analysis. Setting Canada. Participants A purposive sample of PTs who managed clients with knee symptoms and/or diagnosed knee OA in community/outpatient settings in three provinces in Canada (Ontario, Alberta, British Columbia). Results Factors that affected physical therapy management of early knee OA were identified at four levels: the community, healthcare system, healthcare provider and client level. Some healthcare provider factors acted primarily as enablers of management, such as PTs’ confidence in their ability to manage perceived early knee OA, PTs’ beliefs about consequences of OA and the PT scope of practice. However, the study illuminated a range of modifiable factors that can act as barriers to management. These factors included access to services in the community and healthcare system; healthcare provider factors such as time, access to evidence and physician’s role in referrals and messaging; and client factors related to client characteristics (eg, general health, socioeconomic status), engagement in management and beliefs about OA. Conclusion These findings provide us with a basis to begin to address specific barriers and to optimise care for early knee OA.

https://pharmrev.aspetjournals.org/content/pharmrev/72/1/218.full.pdf

Pharmacology and Therapeutics of Bronchodilators Revisited.

There is increasing interest in the origins of chronic obstructive pulmonary disease (COPD), as it is envisaged that preventive efforts and treatment can modify its clinical course. The concept of early COPD is not new, but it has recently regained interest, given new population data, recent cellular and molecular advances and insights from clinical trials. To date, many knowledge gaps in the nature of early COPD still exist, mainly because COPD has always been considered a disease of the elderly, and little attention has been paid to the pathological changes occurring in the lungs of individuals at risk before they develop clinically evident COPD. Future studies should focus on identifying early pathological manifestations of COPD in order to prevent its progression in susceptible individuals. In this review, we aim to summarise what is known on early COPD, from the epidemiological, cellular and clinical perspectives.

https://erj.ersjournals.com/content/erj/52/6/1801448.full.pdf

What is early COPD and why is it important

Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood. We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes. We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed. These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.

/pdf/gut-microbiota-dysbiosis-contributes-to-the-development-of-298n5q28mt.pdf

Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.

BackgroundPatients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. MethodsIn a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 μg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in...

Minjing Li

Papers

Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease