Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation.

Household air pollution caused by inefficient cooking practices causes 4 million deaths a year worldwide. In Nepal, 86% of the rural population use solid fuels for cooking. Over 25% of premature deaths associated with air pollution are respiratory in nature. Here we aimed to identify molecular signatures of different cookstove and fuel type exposures in human airway epithelial cells, to understand the mechanisms mediating cook stove smoke induced lung disease. Primary human airway epithelial cells in submerged culture were exposed to traditional cook stove (TCS), improved cook stove (ICS) and liquefied petroleum gas (LPG) stove smoke extracts. Changes to gene expression, DNA methylation and hydroxymethylation were measured by bulk RNA sequencing and HumanMethylationEPIC BeadChip following oxidative bisulphite conversion, respectively. TCS smoke extract alone reproducibly caused changes in the expression of 52 genes enriched for oxidative stress pathways. TCS, ICS and LPG smoke extract exposures were associated with distinct changes to DNA methylation and hydroxymethylation. A subset of TCS induced genes were associated with differentially methylated and/or hydroxymethylated CpGs sites, and enriched for the ferroptosis pathway and the upstream regulator NFE2L2. DNA methylation and hydroxymethylation changes not associated with a concurrent change in gene expression, were linked to biological processes and molecular pathways important to airway health, including neutrophil function, transforming growth factor beta signalling, GTPase activity, and cell junction organisation. Our data identified differential impacts of TCS, ICS and LPG cook stove smoke on the human airway epithelium transcriptome, DNA methylome and hydroxymethylome and provide further insight into the association between indoor air pollution exposure and chronic lung disease mechanisms.

Patient-related outcomes in patients referred to a respiratory clinic with persisting symptoms following non-hospitalised COVID-19.

Survivors of COVID-19 can present with varied and persisting symptoms, regardless of hospitalisation. We describe the ongoing symptoms, quality of life and return to work status in a cohort of non-hospitalised COVID-19 survivors with persisting respiratory symptoms presenting to clinic, who consented and completed patient-reported outcome measures. We identified fatigue, reduced quality of life and dysregulated breathing alongside the breathlessness. Those with co-existent fatigue had worse mood and quality of life and were less likely to have returned to normal working arrangements compared to those without fatigue. For non-hospitalised people with persisting symptoms following COVID-19 referred to a respiratory assessment clinic, there was a need for a wider holistic assessment, including return to work strategies.

The feasibility and tolerability of using inspiratory muscle training with adults discharged from the hospital with community-acquired pneumonia.

INTRODUCTION: Patients experience substantial morbidity following discharge from hospital and during recovery from communi-ty-acquired pneumonia (CAP). Inspiratory muscle training (IMT) has demonstrated improved functional capacity and reduced patient-reported symptoms. To date the safety and tolerability of these methods have not been determined in CAP patients recovering following hospitalization. Accordingly, this study aimed to assess the safety and tolerability of IMT in adults discharged from hospital with CAP. MATERIAL AND METHODS: Participants received an IMT device (POWERbreathe KHP2) and completed 9-weeks IMT training with weekly follow-up. Frequency (twice daily) and load (50% PImax) were fixed throughout, but training volume increased incrementally (2-week habituation phase, 7-week training phase). Primary outcomes of interest included IMT safety and tolerability. RESULTS: Twenty-two participants were recruited; 16 were male, mean age 55.2 years (range 27.9-77.3). From 1183 possible training days, side effects were reported on 15 occasions by 10 individual participants. All reported side-effects were assessed as grade 1 and did not prevent further training. Participant-reported IMT acceptability was 99.4%. CONCLUSION: Inspiratory muscle training is safe and tolerable in patients following hospitalisation for CAP. Patient satisfaction with IMT is high and it is viewed by patients as being helpful in their recovery. Distinguishing CAP-related symptoms and device-related side effects is challenging. Symptom prevalence declined during follow-up with concurrent improvements in spirometry observed. Further research is required to determine the efficacy of IMT interventions following CAP and other acute respiratory infections.

Management of Fracture Risk in Patients with Chronic Obstructive Pulmonary Disease (COPD): Building a UK Consensus Through Healthcare Professional and Patient Engagement.

Introduction: Osteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD. Methods: A systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like. Results: The surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required. Conclusion: There is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required.

Thorax in focus: chronic obstructive pulmonary disease.

Keeping up to date with scientific developments in any field of medicine is challenging, and chronic obstructive pulmonary disease (COPD) is no exception. Thorax has played an important part in the communication of key developments to its readership. In this article we review original research published in the journal over the last 2-3 years. We consider scientific and clinical developments in the epidemiology, mechanisms and treatment of COPD, placing these articles in the context of other relevant literature in COPD.