Type 2 inflammation and biological therapies in asthma: targeted medicine taking flight

The field of asthma has undergone a dramatic change in recent years. Advances in our understanding of type 2 airway inflammation have driven the discovery of monoclonal antibodies targeting specific aspects of the immune pathway. In landmark trials, these drugs have shown efficacy in reducing asthma attacks and exposure to oral corticosteroids, important causes of morbidity in people with asthma. Our review explores the key features of type 2 inflammation in asthma and summarizes the clinical trial evidence of the novel monoclonal antibody treatments and future avenues for treatment

Obstructive sleep apnoea: a cause of chronic cough

Chronic cough is a common reason for presentation to both general practice and respiratory clinics. In up to 25% of cases, the cause remains unclear after extensive investigations. We report 4 patients presenting with an isolated chronic cough who were subsequently found to have obstructive sleep apnoea. The cough improved rapidly with nocturnal continuous positive airway pressure therapy. Further studies are required to investigate the prevalence of coexistence of these common conditions

How have we measured trial outcomes of asthma attack treatment? a systematic review

Background Asthma attacks are a common problem for people with asthma and are responsible for significant healthcare costs. There is interest in a precision medicine approach to treatment. However, the choice of trial outcome measures for asthma attack treatment is hampered by the absence of a consensus on suitability. We carried out a systematic review to understand the characteristics of outcome measures used in randomised controlled trials of asthma attack treatment. Have randomised controlled trials of asthma attack treatment measured outcomes that are useful to patients and healthcare providers? Methods The protocol was registered on PROSPERO (CRD42022311479). We searched for randomised controlled trials comparing treatments for adults with asthma attacks, published in English between 1972 and 2022 on MEDLINE, Embase and Cochrane Library databases. We recorded the outcome measures and study characteristics. Results We identified 208 eligible randomised controlled trials from 35 countries. Trials ranged from 12 to 1109 participants, with a median of 60. The most common settings were the emergency department (n=165) and hospital admission (n=33). Only 128 studies had primary and secondary outcomes defined clearly. In those that did, 73% of primary outcomes measured change in lung function or other physiological parameters over a short period (usually \u3c 24 h). Patient-reported and healthcare utilisation outcomes were the primary outcome in 27%. Conclusions Outcomes in randomised controlled trials of asthma attack treatment focus on short-term changes in lung function and may not capture patient-centred and economically important longer-term measures. More work is needed to investigate patient and other stakeholder preferences on core outcome sets

The assessment of quality of life in acute cough with the Leicester Cough Questionnaire (LCQ-acute)

INTRODUCTION: Acute cough has a significant impact on physical and psychosocial health and is associated with an impaired quality of life (QOL). The Leicester Cough Questionnaire (LCQ) is a validated cough-related health status questionnaire designed for patients with chronic cough. The purpose of this study was to validate the LCQ for the assessment of health related QOL in patients with acute cough and determine the clinical minimal important difference (MID). METHODS: 10 subjects with cough due to acute upper respiratory tract infection underwent focused interviews to investigate the face validity of the LCQ. The LCQ was also evaluated by a multidisciplinary team. 30 subjects completed the revised LCQ-acute and a cough visual analogue score (VAS: 0-100 mm) within one week of onset of cough and again 0.9. There was a significant correlation between LCQ-acute and VAS (ρ = -0.48, p = 0.007). The LCQ-acute and its domains were highly responsive to change; effect sizes 1.7-2.3. The MID for total LCQ and VAS were 2.5 and 13 mm respectively. CONCLUSION: The LCQ-acute is a brief, simple and valid instrument to assess cough specific health related QOL in patients with acute cough. It is a highly responsive tool suggesting that it will be particularly useful to assess the effect of antitussive therapy

Derivation of a prototype asthma attack risk scale centred on blood eosinophils and exhaled nitric oxide

Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide. Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1-2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment

Severe T2-high asthma in the biologics era: European experts' opinion

The European Respiratory Biologics Forum gathered participants from 21 countries in Madrid, Spain, to discuss the management and treatment of severe asthma in the era of biologics. The current insights on the pathophysiology of severe asthma were discussed, as well as the role of respiratory biologics in clinical practice and strategies for eliminating chronic use of oral corticosteroids. The participants also highlighted the key challenges in identifying patients with severe asthma based on phenotypes, biomarkers and treatable traits, and the existing problems in patient referral to specialist care. The monitoring of treatment was debated and the need for a change towards precision medicine and personalised care was emphasised throughout the meeting. This review provides a summary of the discussions and highlights important concerns identified by the participants regarding the current management of severe asthma

First maintenance therapy for COPD in the UK between 2009 and 2012 : a retrospective database analysis

This research was conducted by Research in Real-Life Ltd (Cambridge, UK), an independent company. Medical writing support was provided by Tracey Lonergan on behalf of Complete Medical Communications and was funded by Almirall S.A. Funding This research was funded by Almirall S.A.Peer reviewedPublisher PD

Theobromine for the treatment of persistent cough: A randomised, multicentre, double-blind, placebo-controlled clinical trial

© Journal of Thoracic Disease. Background: To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods: This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results: At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P < 0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions: This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration: ClinicalTrials.gov: NCT01656668

A retrospective cohort study in severe asthma describing commonly measured biomarkers: Eosinophil count and IgE levels.

Background: Identifying asthma patients suitable for biologic therapy includes the assessment of blood biomarkers (IgE and eosinophils (EOS)). How they relate to each other is unclear. Methods: This retrospective, database study used routinely collected clinical data to identify and evaluate an asthma cohort (classification code for asthma; ≥ 18 years; ≥1 prescription for asthma; ≥1 estimation of serum IgE, in 2 years prior to index date). Distribution into high and low IgE and EOS groups (IgE cut-point: &gt; or ≤75 kU/L; EOS cut point: &gt;or ≤400 μ/L), and characteristics by group are described. Findings: In patients with severe asthma (British Thoracic Society Step (BTS) ≥4; N = 884), using maximum recorded IgE/EOS, 33% had high IgE/high EOS, 28% low IgE/low EOS and approximately a fifth each had high IgE/low EOS or low IgE/high EOS. Proportions were similar when EOS values measured 2 or 4 weeks before an exacerbation were excluded. Using EOS/IgE ′same day’ measurements (N = 578) only identified half of the high EOS group. Patients in high IgE groups were more likely to be younger males without comorbid COPD; those in high EOS groups were more likely to be on BTS treatment Step 5 vs 4. The low IgE/low EOS group had the lowest incidence of asthma-related hospital attendances, the highest incidence was observed in the high EOS groups. Conclusion: Maximum available EOS measurement irrespective of exacerbations may be relevant when considering therapy. These data showed low IgE/Low EOS to be more benign and high EOS groups at increased risk of frequent, severe exacerbations