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Continuous non-invasive ventilation in patients with neuromuscular disease: tracheostomy can be avoided (mostly)
For patients with neuromuscular diseases (NMD) and a high level of ventilatory dependence requiring continuous non-invasive ventilatory support (CNVS) and mechanical insufflation-exsufflation (MI-E), tracheostomy mechanical ventilation (TMV) is recommended in some guidelines. Improved clinical management and ventilator and chest clearance strategies has led to some patients avoiding tracheostomy even when unable to perform any ventilator-free breathing. Gonçalves et al (Pulmonology 2021;27:509) reported the first multicentre study (19 centres from 16 countries) of CNVS plus MI-E use in 1623 patients with amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD) or spinal muscular atrophy type 1 (SMA1). Nearly half (761/1623) progressed to CNVS dependence with no ventilator-free breathing, proceeding to survive a further combined 2218 patient-years without tracheostomy. The most common patient group to procced to tracheostomy were patients with advanced bulbar ALS with stridor, low peak cough flow generated by MI-E and O2 saturation below 95% despite CNVS. In patients with DMD and SMA1 who required intubation for acute respiratory failure the authors reported a ~99% extubation success rate (with CNVS and MI-E protocol) in previously described ‘unweanable’ patients. The authors comment that a dedicated multidisciplinary team and a well-structured extubation protocol are essential to deliver these results. Therefore, they aim to endorse the CNVS and MI-E protocol as a safe alternative to TMV in NMD patients, even if unable to perform ventilator-free breathing.
Spirometric restriction in adulthood: the damage may occur early in life
Restrictive spirometry is a predictor of morbidity and mortality in adults and its prevalence is elevated in regions where maternal and child undernutrition are major public health concerns. However, little data are available to examine underlying risk factors for development of restrictive spirometry. Voraphani et al (Lancet 2022;10:59) performed the first analysis of lung restriction and nutrition interaction, using data prospectively collected since birth. They studied subgroups of three birth cohorts: 652 participants from Tucson Children’s Respiratory Study (USA), 1817 from Swedish Child (Barn), Allergy, Milieu, Stockholm, Epidemiological survey and 411 from UK Manchester Asthma and Allergy Study. These studies applied health questionnaires through childhood and adulthood including demographic, anthropometric, nutritional and also parental information. Spirometry at adulthood (between age 18 and 36 years) was the main outcome. Adulthood spirometric restriction (defined by reduced forced vital capacity (FVC) (<10th percentile) with a preserved forced expiratory volume in 1 s/FVC ratio (≥10th percentile)). Multivariate models demonstrated that independent predictors of adulthood spirometric restriction included: maternal nutritional pregnancy problems (relative risk (RR) 2.48, 95% CI 1.30 to 4.76, p=0.0062); born small for gestational age, <10th percentile (RR 3.26, 95% CI 1.34 to 7.93, p=0.0093) and childhood underweight, body mass index-for-age <5th percentile (RR 3.54, 95% CI 1.35 to 9.26, p=0.010). Body composition data were available for a subset of subjects which indicated that the risk was related to lean body mass deficit. These data underline the consequences of undernutrition in the gestational period and throughout childhood with more data needed on interventions that could alter outcomes in this area.
Itepekimab in moderate to severe asthma: another promising but unpronounceable monoclonal antibody treatment
Monoclonal antibody therapies targeting Th2 inflammation mediators have demonstrated a significant impact in asthma management. Itepekimab, a subcutaneous anti-interleukin-33 monoclonal antibody, was developed following studies which have shown that interleukin-33 is associated with asthma susceptibility and its potential clinical utility has been supported by mouse models. Wechsler et al (NEJM 2021;385:1656) performed a multicentre, double-blind, proof-of-concept phase 2 trial of itepekimab in adult patients with asthma on combined inhaled corticosteroids and long-acting beta-agonist maintenance therapy with a history of at least one severe exacerbation in the preceding 12 months. An active comparator group with dupilumab was also evaluated due to the potential synergistic effects on the Th2 inflammatory pathway. The primary outcome was an event indicating loss of asthma control. Patients had a 4-week run-in period on usual therapy, followed by initiation of the trial intervention (weeks 0–12). A taper of pretrial maintenance therapy (weeks 6–9) occurred alongside the trial intervention and was restarted during the follow-up period (weeks 12–32). A total of 296 patients were randomised into 4 groups and 281 concluded the trial: itepekimab (n=72), itepekimab +dupilumab (n=71), dupilumab (n=67) and placebo (n=71). A significantly lower incidence of loss of asthma control was identified in the itepekimab group vs placebo group (OR 0.42 95% CI 0.20 to 0.88, p=0.02). Secondary outcomes of improved lung function and asthma related quality of life scores were also improved. There was a similar adverse effect profile compared with placebo. No additional beneficial effect was verified in the itepekimab +dupilumab group. The authors concluded that itepekimab is a safe therapy with potential for clinical benefit in patients with moderate to severe asthma.
Cold-inducible RNA-binding protein: a promising biomarker in idiopathic pulmonary fibrosis
Despite new therapies for idiopathic pulmonary fibrosis (IPF) the overall prognosis remains limited but with significant variation. Early identification of patients at high risk for disease progression and mortality could lead to improve clinical decision making. Cold-inducible RNA-binding protein (CIRBP) is a stress response protein involved in inflammation and fibrogenesis that is highly expressed in fibrotic areas of IPF patient’s lungs. Hozumi et al (Chest 2021;160:2149) evaluated the role of CIRBP as a biomarker of disease progression or death in IPF in two independent retrospective cohorts of patients with IPF (n=95 and n=93) and without other significant life limiting pathology. CIRBP was analysed in samples stored at the time of diagnosis with outcomes analysed for at least 1 year or until death. Disease progression was defined as a ≥10% %FVC decline. They determined the optimal cut-off value of CIRBP in cohort 1 (derivation) and applied this to cohort 2 (validation). Patients with high CIRBP had more 1-year disease progression (62.5% vs 26.8% in cohort 1, p=0.0027% and 66.7% vs 33.3% in cohort 2, p=0.0075) and higher mortality comparing with patients with low CIRBP. Of note the predictive use of CIRBP appeared independent of anti-fibrotic treatment and was greatest in early-stage disease. The authors concluded that CIRBP is a potential independent predictor of disease progression but that further data are needed to enable its use to facilitate therapeutic decisions.
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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.