Daily Respiratory Research Analysis

BACKGROUND: The benefits and harms of patient-facing digital inhalers (inhalers with a sensor providing patients immediate feedback on adherence and technique) for asthma remain unclear. OBJECTIVE: To systematically synthesize treatment outcomes of patient-facing digital inhalers for asthma. METHODS: As part of developing upcoming American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters severe and difficult-to-control asthma guidelines, we searched MEDLINE, Embase, CENTRAL, CINAHL, PsycINFO, International Clinical Trials Registry Platform (ICTRP), and Latin American and Caribbean Literature on Health Sciences (LILACS), and monitored for additional studies to April 1, 2025, for randomized controlled trials evaluating patient-facing digital inhalers in asthma. Paired reviewers independently screened records and extracted data. Individual patient-level data in random effects analysis of covariance models addressed asthma control and asthma-related quality of life. Random-effects meta-analyses addressed severe exacerbations and harms. We used the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach to assess certainty of evidence (PROSPERO CRD42024525051). RESULTS: Twelve trials enrolled 2,483 children (aged 4-17 y) and adults with asthma. Patient-facing digital inhalers probably improve asthma control (Asthma Control Test, mean difference 0.63 [95% confidence interval {95% CI} 0.29-0.96]; 44.3% vs 39.8% achieving a 3-point increase, moderate certainty) and may reduce severe exacerbations in patients at high risk for future exacerbations (risk ratio 0.89 [95% CI 0.69-1.16]; risk difference 45 fewer per 1,000 [95% CI 127 fewer to 66 more per 1,000], low certainty), with little to no difference in asthma-related quality of life (low certainty). The median of mean device failure rate was 12%, with trials reporting issues regarding sensor synchronization with smartphones (very low certainty). One trial reported a protected health information exposure while using patient-facing digital inhalers. CONCLUSIONS: Patient-facing digital inhalers probably improve asthma control and may reduce severe asthma exacerbations in patients at high risk for future exacerbations with minimal harm.

BACKGROUND: Rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in idiopathic pulmonary fibrosis (IPF). We aimed to assess whether rare qualifying variants in monogenic adult-onset pulmonary fibrosis genes are associated with IPF survival. Using polygenic risk scores (PRS), we also evaluated the influence of common IPF risk variants in patients carrying the qualifying variants. METHODS: We identified qualifying variants in telomere and non-telomere genes using whole-genome sequences from individuals clinically diagnosed with IPF and enrolled in the Pulmonary Fibrosis Foundation Patient Registry (PFFPR), a large multicentre, observational cohort study (March 29, 2016 to June 15, 2018, n=888). We also derived a PRS for IPF (PRS-IPF) from known common sentinel IPF variants. The primary outcome was the association between qualifying variants and survival. The secondary outcome was the association between qualifying variants and PRS-IPF. We used logistic regression models adjusted for sex, age at diagnosis, and principal components of genetic heterogeneity to examine the mutual relationship of qualifying variants and PRS-IPF. The association between qualifying variants and PRS-IPF with survival was tested using Cox proportional hazard models adjusted for baseline confounders. Validation of the results was sought in data from an independent multicentre, prospective, observational cohort study of IPF in the UK (PROFILE, May 17, 2010 to Sept 5, 2017, n=472), and results were meta-analysed under a fixed-effects model.

BACKGROUND: Tuberculosis (TB) incidence and mortality in people living with HIV can be reduced by TB preventive treatment (TPT). However, low levels of screening and uptake, poor adherence, and loss to follow-up considerably reduce its effectiveness. We therefore aimed to assess the losses within all steps of the screening and treatment cascade. METHODS: We carried out a comprehensive, global systematic review of the TPT cascade of care in people living with HIV (PROSPERO: CRD42020162396). To enhance data generalisability we included articles which reported the proportion of people living with HIV completing any step of the TPT cascade in low and high TB burden countries published before March 2024. Random effects meta-analysis produced pooled estimates of the proportion proceeding to the next step along the cascade. Results were explored through subgroup analyses and meta-regression. RESULTS: Data from 368 cohorts containing 2.7 million participants were included. High levels of heterogeneity in outcomes were seen. Most participants were from Africa (80.6%). Isoniazid monotherapy was used for TPT in 92.6% of cohorts, usually for 6 months. Substantial loss to follow-up was found throughout the treatment cascade, with more than one in six patients lost at the following steps: initial screening, immunological testing, treatment start and completion. Regimens lasting <6 months had higher completion rates (88.4%) than those lasting 6-9 months (74.4%) or >9 months (61.6%). CONCLUSIONS: Our analysis highlights substantial loss to follow-up at multiple steps during the care cascade. This may significantly lower the reported effectiveness of TPT in real-world settings. Research and policy should focus on simplified care pathways and novel, shorter treatment regimens that optimise retention in care.