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Follow the stars: blood eosinophil-directed treatment of COPD exacerbations
Oral corticosteroids (OCS) have been the acute treatment for COPD exacerbations for decades based on small trials primarily conducted in inpatients. But OCS have devastating long-term risks that increase cumulatively with dose. Ramakrishnan and colleagues (Lancet Respiratory Medicine 2023, DOI: 10.1016 /S2213-2600(23)00298-9) tested whether blood eosinophil-directed prednisolone treatment (BET) was non-inferior to standard treatment with prednisolone (ST) in this multicentre, double-blind, randomised, placebo-controlled trial (STARR2). In 14 UK-based general practices, 144 COPD exacerbations from 93 participants were randomised equally to BET or ST. All patients also received oral antibiotics. The primary outcome was the rate of treatment failure (re-treatment with antibiotics or steroids, hospitalisation for any cause, or death, assessed at 30 days). An upper margin of 1.105 for the 95% CI was defined as the non-inferiority margin to capture 75% of the benefit obtained from standard care. There were 14 (19%) treatment failures at 30 days post-exacerbation in the blood eosinophil-guided group and 23 (32%) in the standard care group, confirming non-inferiority (RR 0.60 [95% CI 0.33 to 1.04]. The combined treatment failure prednisolone dose was 1620 mg in the BET group vs 3450 mg in the ST group. The practice-changing STARR2 trial conclusively shows that biomarker-directed treatment of non-hospitalised COPD exacerbations is safe and reduces exposure to oral corticosteroids.
Food for thought: nutritional support for household contacts of patients with pulmonary tuberculosis
Tuberculosis remains a global health problem that is closely linked to deprivation. Undernutrition is common, increasing the risk of mortality, drug toxicity, delayed sputum conversion, and recurrence. Bhargava and colleagues (Lancet 2023, DOI: 10.1016 /S0140-6736(23)01 231 X) conducted a field-based, cluster-randomised controlled trial evaluating nutritional support for household contacts of patients with microbiologically confirmed pulmonary tuberculosis on tuberculosis incidence (RATIONS). The study team in India identified 10 345 household contacts related to 2800 patients with microbiologically confirmed tuberculosis. Index tuberculosis patients in both groups received a monthly food basket with 1200 kcal and 52 grams of protein per day and micronutrient pills ($13 per month). Household contacts in the intervention group received a food basket providing 750 kcal and 23 grams of protein per day ($4.75 per month) for the duration of tuberculosis treatment. 5328 participants in the intervention group and 4283 participants in the control group completed the primary outcome assessment. After 2 years follow-up, there were 122 incident tuberculosis cases in the control group (2.6%, 95% CI 2.2 to 3.1; incidence rate 1.27 per 100 person-years) and 96 incident cases in the intervention group (1.7%, 1.4–2.1; 0.78 per 100 person-years). There was a relative reduction of microbiologically confirmed tuberculosis incidence of 48% in the intervention group. Approximately 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis. This is a feasible, low-cost intervention that could reduce tuberculosis incidence in countries with high levels of tuberculosis and undernutrition.
Bystander or mediator: the airway microbiome, environmental exposure, and respiratory health
Exposure to environmental toxicants, including cigarette smoke, biofuel, and pollution, causes airway inflammation and may alter the airway microbiome. Lin and colleagues (Nature Medicine 2023, DOI: 10.1038 /s41591-023-02424-2) used a province-wide COPD surveillance programme in China to cross-sectionally sample induced sputum from adults aged 40–81 years. After exclusion of participants with recent antibiotic use, 1651 participants had bacterial 16S rRNA gene sequencing, 719 had fungal internal transcribed spacer sequencing, and 1128 had metagenomic sequencing. Geographic district had the strongest contribution to the variation in microbiome profiles, 10.9 fold greater than smoking, the second highest association. Smoking was mainly associated with bacterial variation, while PM2.5 concentration was predominantly associated with fungal variation. Certain bacterial genera may mediate the association between smoking and FEV1/FVC, and occupational pollution with COPD Assessment Test (CAT) score. Some fungal taxa may mediate the association between PM2.5 concentration and FEV1/FVC. The authors derived an airway microbiome health index that declined in disease and found an expansion in bacterial and fungal interaction from healthy, to pre-COPD, to COPD, with the bacterial taxa driving the transition. The study advances our understanding of the association of the airway microbiome with environmental exposure, health outcomes and respiratory disease. There may be utility in targeting the microbiome for risk prevention, however the huge variation of the microbiome with geography could make this challenging.
Strengthening the case to vaccinate: RSV infection during infancy and asthma during childhood
Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in infants worldwide. Previous studies of RSV infection in infancy and development of childhood asthma are confounded because they did not include a control group of children without RSV infection in infancy. Rosas-Salazar and colleagues (Lancet 2023, DOI: 10.1016 /S0140-6736(23)00811-5) conducted a population-based, prospective birth cohort of healthy infants with born at term across 11 paediatric practices in Tennessee, USA. Children were recruited so that they were 6 months or younger at the beginning of their first RSV season. They identified RSV infection status actively by collecting a nasal wash for RSV PCR if the child had an acute respiratory infection. Additionally, they measured RSV serum antibody titres by ELISA at age 1 year. Children were classified as not infected or infected with RSV in the first year of life and followed up for 5 years. The primary outcome included asthma diagnosis or asthma medication use at 5 years of age, termed ‘5 year current asthma’. 1946 children enrolled and 1741 were assessed for RSV infection at 1 year. The proportion of children with RSV infection during infancy was 944 (54%; 95% CI 52 to 57%). The proportion of children with 5 year current asthma was lower in those without RSV infection during infancy (91 [16%] of 587) than those with RSV infection during infancy (139 [21%] of 670; p=0·016). Severity of RSV infection was associated with increased risk of asthma. Interestingly, RSV was more associated with non-atopic asthma than atopic asthma. RSV vaccination in pregnancy, or RSV monoclonal antibody treatment in infants, may prevent, delay, or decrease the severity of RSV infection and reduce the prevalence of childhood asthma.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.