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Persistent airflow limitation in asthma: not exclusive to those with severe disease and linked with exacerbations
Persistent airflow limitation (PAL) is an asthma phenotype defined as airflow obstruction that remains after the use of a β2-agonist. Past studies on PAL have included small populations and were mostly restricted to severe asthma. Kole et al (Lancet Respir Med 2023;11:55) conducted a post hoc analysis to investigate the determinants and outcomes of PAL in patients with asthma who were included in the Assessment of Small Airways Involvement in Asthma (ATLANTIS) study, a multicentric cohort with 1-year follow-up. PAL was defined by authors as a postbronchodilator FEV1/FVC less than the lower limit of normal at baseline and was identified in 33% of the 760 patients in ATLANTIS. PAL was an independent predictor of exacerbations (HR 1.73, 95% CI 1.22 to 2.48) and was associated with an earlier diagnosis, current smoking and markers of eosinophilic inflammation. In addition, PAL was identified in 21% of those classified as Global Initiative for Asthma (GINA) steps 1–2 (ie, mild asthma), in whom it was also an independent predictor of exacerbations (HR 5.55, 95% CI 1.83 to 16.86). In severe asthma, patients with PAL have been shown to respond well to add-on treatment with long-acting muscarinic antagonists. Despite the potential confounding inherent to post hoc analyses, these results suggest that patients with mild asthma (GINA step 1–2) with PAL could benefit from increased treatment intensity to reduce the risk of exacerbations.
Alpha-1-antitrypsin deficiency: increased risk for both hepatic and non-haptic cancers
Alpha-1-antitrypsin deficiency (AATD) is an established risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is less well studied. Hiller and colleagues (Eur Respir J 2022;60:2103200) used the longitudinal Swedish National AATD Register to evaluate the incidence of cancer in 1570 patients with AATD (phenotype PiZZ). The control population (n=5951) consisted of non-AATD individuals from population-based cohorts within the Obstructive Lung Disease Studies in Northern Sweden studies. Patients with previous lung/liver transplant or previous cancer in the last 5 years were excluded from analysis. Patients with AATD had higher incidence of both hepatic (HR 20.34; 95% CI 8.83 to 46.86; p<0.001) and non-hepatic cancer (HR 1.25; 95% CI 1.04 to 1.51; p=0.018) compared with controls. This risk remained increased after adjustment for age, sex, smoking habits and liver disease both for hepatic (HR 23.39; 95% CI 9.88 to 55.39) and non-hepatic cancer (HR 1.27; 95% CI 1.05 to 1.53). Survival following a diagnosis of cancer was shorter in PiZZ individuals than controls (6 [4–8] years vs 12 [9–15] years; p=0.003). Although the role of AAT deficiency in the pathogenesis of cancer is unclear, these results support an increased risk of cancer in PiZZ. More work is needed on the potential to actively screen patients with AATD to reduce cancer-related morbidity and mortality.
Oxygen-saturation targets for invasively ventilated patients: high, intermediate or low makes no impact on duration of ventilation
The optimal peripheral oxygen-saturation (SpO2) target for patients undergoing invasive mechanical ventilation (IMV) is unknown with conflict results of previous clinical trials. Semler et al (N Engl J Med 2022;387:1759) conducted an unblinded, randomised, cluster-crossover trial over 36 months in an adult critical care. The 2541 patients were assigned to 3 groups of similar size and characteristics at baseline to compare a lower SpO2 target (88 to 92%), an intermediate target (92 to 96%) and a higher target (96 to 100%) during IMV. The median number of ventilator-free days was similar (p=0.81) in the lower (20, IQR 0 to 25), intermediate (21, IQR 0 to 25) and higher-target (21, IQR 0 to 26) groups. In-hospital death by day 28 was also similar between groups, occurring in 34.8% in the lower, 34.0% in the intermediate and 33.2% in the higher-target group. The incidences of adverse events as cardiac arrest, arrhythmia, myocardial infarction, stroke and pneumothorax were similar in the three groups. Among adults in critical care receiving mechanical ventilation, limiting exposure to supplemental oxygen by targeting SpO2 values as low as 90% does not reduce mortality or expedite liberation from ventilation. These findings are consistent with previous randomised trials, but conflict with the U-shaped relationship reported in observational studies. Critical care physicians should select appropriate targets for SpO2 based on individual patient risk of harm from hypoxaemia or hyperoxia.
Inhaler selection in primary care chronic obstructive pulmonary disease (COPD) management: observation not sufficient to assess suitability for DPI
Poor inhaler technique is associated with worse quality of life for patients with COPD. However, there is little information on best clinical practice to guide dry powder inhaler (DPI) device selection, inhaler technique review or the need to assess peak inspiratory flow (PIF). Leving et al (npj Primary Care Respiratory Medicine 2022:32:59) conducted a cross-sectional observational study over 8 months in six countries (PIFotal study). PIF was objectively assessed with a commercially available device. Inhalation technique was assessed through in-person observation by a primary healthcare professional (HCP) and rated through video by at least two independent HCPs. PIF measurements were available for 1389 patients: 71% were able to generate sufficient inspiratory effort (typical PIF≥device’s optimal), whereas 16% had suboptimal PIF (typical PIF<device’s optimal but maximum PIF≥device’s optimal), and 13% revealed insufficient inspiratory effort (typical and maximum PIF<device’s optimal). There was a discrepancy between observation of an apparently adequate inspiratory technique during inhaler review and the objective measurement of PIF which occurred in 40% of patients. The agreement between in-person inhalation technique observation and video recordings assessments was low (54%), with greater detection of errors in the video assessment. Of note to clinicians, observation alone does not identify all patients with suboptimal/insufficient PIF for their DPI. Also, video assessments seem to detect more inhalation technique errors than observation alone. Whenever possible, the authors recommend objectively assessing the patient’s PIF as well as inhaler technique prior to prescribing a DPI. Patients with inadequate PIF may be switched to an alternative inhaler which do not depend on a patient’s ability to generate sufficient inspiratory flow, namely, a soft mist inhaler or pressurised metered dose inhaler.
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Footnotes
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.