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The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy. Clinical trial registered with clinicaltrials.gov (NCT00692198).

IntroductionDespite strong evidence that maturation patterns of the gut microbiome in early life influence the risk for childhood asthma, very little is known about gut microbiota patterns in adults with established asthma, and of greater interest relationships to phenotypic features that characterise asthma heterogeneity.MethodsFifty-eight faecal samples from 32 adults with (n=24) and without (n=8) asthma were analysed using 16S ribosomal RNA gene sequencing methods to characterise intestinal bacterial composition. Compositional stability of paired samples was evaluated and features of gut bacterial community structure analysed in relation to extensive clinical characterisation data collected from subjects, who were enrolled in a prospective observational cohort study at the University of Michigan.ResultsDifferences in gut bacterial community structure were associated with aeroallergen sensitisation and lung function as assessed by forced expiratory volume in 1 s (FEV1) %predicted. Associations with FEV1 were consistently observed across independent analytic approaches. k-means clustering of the gut microbiota data in subjects with asthma revealed three different clusters, distinguished most strongly by FEV1 (pConclusionIn this pilot study of asthmatic and non-asthmatic subjects, significant relationships between gut microbiota composition, aeroallergen sensitisation and lung function were observed. These preliminary findings merit further study in larger cohorts to explore possible mechanistic links to asthma phenotype.