Digitally monitored inhaled therapy: a 'smart' way to manage severe asthma?

INTRODUCTION: One of the fundamental challenges of managing patients with severe asthma is treatment adherence, particularly with inhaled corticosteroids. Adherence is difficult to measure objectively and poor adherence is associated with worse outcomes. In this study, assess the ability of a 'smart' inhaler to record adherence in severe asthma patients and measure the impact of this on asthma control. METHODS: Consecutive consenting patients meeting criteria for biologics had their existing high-dose ICS/LABA//LAMA combination inhaler/s switched to mometasone/indacaterol/glycopyrronium (114/46/136). Routine clinical data, including blood eosinophils, FeNO, and ACQ-6 scores were collected at baseline and at 4 wk. Adherence was then checked on the Propeller Health app, and good adherence was defined as >80% of prescribed usage. Participants were then followed-up at 12 months to record the proportion of patients who were initiated on biologics. RESULTS: 77 patients (mean [SD] age = 50.4 [15.7] years, 67.5% female [n = 52]) participated. 71 participants were able to use the device and 65% (n = 46) of these attained good asthma control and were not initiated on biologics at 12-month follow-up. Both groups demonstrated a significant reduction in ACQ6 score at follow-up (2.81 vs. 1.92, p < 0.001 and 3.05 vs. 2.60, p < 0.001, respectively), but there was no statistically significant difference in improvement between groups. Patients with optimal adherence also demonstrated a significant reduction in median FeNO at follow-up (47 ppb vs. 40 ppb, p = 0.003). CONCLUSIONS: In severe asthma patients, 'smart' inhalers may represent an effective management tool to improve adherence and asthma control, therefore avoiding the need for patients to commence biological therapies.

Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care.

INTRODUCTION: After puberty, females are more likely to develop asthma and in a more severe form than males. The associations between asthma and sex are complex with multiple intrinsic and external factors. AIM: To evaluate the sex differences in the characteristics and treatment of patients with severe asthma (SA) in a real-world setting. METHODS: Demographic, clinical and treatment characteristics for patients with SA in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD) were retrospectively analysed by sex using univariable and multivariable logistic regression analyses adjusted for year, age and hospital/practice. RESULTS: 3679 (60.9% female) patients from UKSAR and 18 369 patients (67.9% female) from OPCRD with SA were included. Females were more likely to be symptomatic with increased Asthma Control Questionnaire-6 (UKSAR adjusted OR (aOR) 1.14, 95% CI 1.09 to 1.18) and Royal College of Physicians-3 Question scores (OPCRD aOR 1.29, 95% CI 1.13 to 1.47). However, they had a higher forced expiratory volume in 1 second per cent (FEV1%) predicted (UKSAR 68.7% vs 64.8%, p<0.001) with no significant difference in peak expiratory flow. Type 2 biomarkers IgE (UKSAR 129 IU/mL vs 208 IU/mL, p<0.001) and FeNO (UKSAR 36ppb vs 46ppb, p<0.001) were lower in females with no significant difference in blood eosinophils or biological therapy. Females were less likely to be on maintenance oral corticosteroids (UKSAR aOR 0.86, 95% CI 0.75 to 0.99) but more likely to be obese (UKSAR aOR 1.67, 95% CI 145 to 1.93; OPCRD SA aOR 1.46, 95% CI 1.34 to 1.58). CONCLUSIONS: Females had increased symptoms and were more likely to be obese despite higher FEV1% predicted and lower type 2 biomarkers with consistent and clinically important differences across both datasets.

An examination of factorial invariance of the Asthma Control Questionnaire among adults with severe asthma.

BACKGROUND: The Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown. METHODS: Data was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed. RESULTS: A one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p<0.001). However approximate measurement invariance was tenable and any failure to observe strong measurement invariance had minimal impact when comparing mean levels of asthma symptom control between patients of different sexes or ages. Average levels of asthma symptom control were lower for non-Caucasians (p = 0.001), females (p<0.01)and increased with age (p<0.01). Reliability of the instrument was high (over 88%) in all subgroups studied. CONCLUSION: The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.

Long term nitrofurantoin induced interstitial lung disease: a case series and literature review.

BACKGROUND AND AIM: In the UK, prophylactic use of nitrofurantoin is recommended in women who have 3 or more UTI per year. Reported cases of nitrofurantoin-induced pulmonary toxicity are limited and the exact mechanism of chronic nitrofurantoin induced lung reaction is unclear. In England, the national trend for prescribing Nitrofurantoin has gone up significantly in the last 10 years. We reviewed 10 cases of nitrofurantoin-induced pulmonary fibrosis diagnosed in last 8 years at our ILD Service. We aimed to reviewe patient demographics, time to presentation, lung function and imaging characteristics. METHODS: We reviewed our ILD database from the year 2012 to 2020. 10 patients were identified diagnosed as Nitrofurantoin Induced Interstitial Lung Disease. All the cases were reviewed in MDT comprising Radiologists and clinicians with interest for ILD. We documented age, sex, initial renal function, eosinophil count, spirometry and radiology findings. In this case series, we focus on various CT findings and reversibility of radiological abnormality following cessation of Nitrofurantoin. RESULTS: The mean age of our patient cohort is 80 years and all were female. The mean time to presentation from prescription was 17 months. Pre-treatment mean eGFR was 76ml/min/1.73m2.7 out of 10 patients had CT findings of ground glass opacity and traction bronchiectasis. 4 patients were treated with prednisolone. The patients in this series improved symptomatically with or without treatment with steroid following cessation of nitrofurantoin therapy, but irreversible changes in the chest imaging may contribute to long term morbidity. CONCLUSIONS: Cautious counselling should be undertaken prior to nitrofurantoin prescription regardless of renal function.

Improving asthma care through implementation of the SENTINEL programme: findings from the pilot site.

Aim: Short-acting ß2-agonist (SABA) overuse adversely impacts asthma-related outcomes and the environment. The SABA rEductioN Through ImplemeNting Hull asthma guidELines (SENTINEL) programme aims to reduce SABA overuse through supported implementation of an adult asthma guideline, which advocates for a SABA-free maintenance and reliever therapy (MART)-preferred treatment where appropriate, across six primary care networks (PCNs) in the UK. We present findings on patient/disease characteristics, asthma prescribing patterns and exacerbation rates from the pilot PCN. Methods: Patients (aged ≥18 years, prescribed at least one inhaled therapy) and their prescribed asthma treatments were characterised using National Health Service data. Asthma treatments and exacerbations were analysed for three periods: 24‒12 months pre-, 12 months pre- and 12 months post-SENTINEL implementation (November 2020‒January 2021). Results: Of the 2571 registered asthma patients, 33.6% (n=864) underwent an asthma review, of whom 44.7% (n=386) were transitioned to MART. Fewer patients were prescribed three or more SABA canisters per year post-implementation in the overall asthma population (45.4% and 46.2% during 24‒12 months and 12 months pre-implementation, respectively, and 23.9% 12 months post-implementation), and in the two subgroups: 1) those who had an asthma review (74.5% and 83.6% during 24‒12 months and 12 months pre-implementation, respectively, and 26.5% post-implementation); and 2) those transitioned to MART following a review (76.4% and 86.5% during 24‒12 months and 12 months pre-implementation, respectively, and 16.3% post-implementation). A higher proportion of patients were exacerbation-free post-implementation in the overall asthma population and in the two subgroups. At least 71.5% of patients transitioned to MART were still prescribed MART 12 months post-implementation, of whom ≥86.7% were SABA-free. Conclusion: SENTINEL implementation led to reduced SABA prescribing, increased inhaled corticosteroid uptake and fewer asthma exacerbations. MART was considered appropriate for ∼50% of reviewed patients, with improved prescribing patterns sustained post-implementation.

It is time to end our love affair with short-acting ß2-agonists in asthma.

In this issue of ERJOR, Noorduynet al. add data to the growing literature showing that SABA overuse in asthma is both common and associated with severe exacerbations. It is time to take note and act to tackle this global issue. https://bit.ly/3BfwhfS.

Outcomes and characteristics of COVID-19 patients treated with continuous positive airway pressure/high-flow nasal oxygen outside the intensive care setting.

BACKGROUND: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been used to manage hypoxaemic respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia. Limited data are available for patients treated with noninvasive respiratory support outside of the intensive care setting. METHODS: In this single-centre observational study we observed the characteristics, physiological observations, laboratory tests and outcomes of all consecutive patients with COVID-19 pneumonia between April 2020 and March 2021 treated with noninvasive respiratory support outside of the intensive care setting. RESULTS: We report the outcomes of 140 patients (mean±sd age: 71.2±11.1, 65% male (n=91)) treated with CPAP/HFNO outside of the intensive care setting. Overall mortality was 59% and was higher in those deemed unsuitable for mechanical ventilation (72%). The mean age of survivors was significantly lower than those who died (66.1 versus 74.4 years, p<0.001). Those who survived their admission also had a significantly lower median Clinical Frailty Score than the non-survivor group (2 versus 4, p<0.001). We report no significant difference in mortality between those treated with CPAP (n=92, mortality: 60%) or HFNO (n=48, mortality: 56%). Treatment was well tolerated in 86% of patients receiving either CPAP or HFNO. CONCLUSIONS: CPAP and HFNO delivered outside of the intensive care setting are viable treatment options for patients with hypoxaemic respiratory failure secondary to COVID-19 pneumonia, including those considered unsuitable for invasive mechanical ventilation. This provides an opportunity to safeguard intensive care capacity for COVID-19 patients requiring invasive mechanical ventilation.

COVID-19 progression, frailty, and use of prolonged continuous positive airway pressure as a ward-based treatment: Lessons to be learnt from a case.

Coronavirus disease 19 (COVID-19) poses the greatest public health threat in 100 years, with cases rising rapidly in many countries around the world. We report a case of a 78-year-old female who exhibited a biphasic course of COVID-19; showing initial clinical improvement followed by deterioration before making a full recovery. The patient was managed with prolonged continuous positive airway pressure (CPAP) and supportive care. In total, 24 days of treatment with CPAP was administered. We emphasize the role of CPAP in the management of severely hypoxemic patients who are inappropriate for mechanical ventilation and describe the role of adequate nutrition and hydration for such patients.

The impact of the first COVID-19 surge on severe asthma patients in the UK. Which is worse: the virus or the lockdown?

Asthma therapy, including monoclonal antibodies, was not associated with #COVID19 infection or hospitalisation in a UK severe asthma population. Shielding led to a reported worsening of mental health in nearly half of patients contacted (47%). https://bit.ly/3jImUsG.

Impact of COVID-19 on COPD and asthma admissions, and the pandemic from a patient's perspective.

There has been a significant reduction in all-cause and exacerbation-related #asthma and #COPD admissions during the #COVID19 pandemic. Patients also report a subjective decline in disease control and describe a negative impact on their mental health. https://bit.ly/2Kv0O0H.

Objective Assessment of Cough: An Early Marker of Response to Biological Therapies in Asthma?

Cough is an important symptom of asthma. The objective assessment of chronic cough has been enhanced by the development of ambulatory cough monitoring systems. Mepolizumab has been demonstrated to reduce exacerbations in eosinophilic asthmatics long-term. We evaluate the utility of objective cough count as an outcome measure in severe eosinophilic asthma treated with mepolizumab. Consecutive, consenting patients initiated on treatment with mepolizumab had a 24-h cough count recorded at baseline; this was repeated at 1, 3 and 6 months. Asthma control questionnaire (ACQ) scores and exacerbation frequency were also recorded. The mean 24-h cough count in 11 subjects (8 females, mean age 53.6 years) was 172.4 at baseline; at 1, 3 and 6 months following initiation of treatment this decreased to 101.4, 92 and 70.8, respectively (p < 0.02). Significant improvements were also observed in mean ACQ score (3-1.6, p < 0.01) and exacerbation frequency (5.5 per year - 1.3, p < 0.01). Objective cough measurement could be used as an early, precise and clinically relevant endpoint in assessing response to asthma therapy.

Suppression of F ENO with observed inhaled corticosteroid therapy in severe asthma: is it a useful test in clinical practice?

F ENO suppression testing is practical and feasible during assessment for biologics in severe asthma. Patients with significant F ENO suppression were less likely to be recommended biologics but saw similar reductions in exacerbation frequency. http://bit.ly/35oSoxP.

Profile of tezacaftor/ivacaftor combination and its potential in the treatment of cystic fibrosis.

Cystic fibrosis (CF) is a life-limiting autosomal recessive disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Management of CF has traditionally relied upon managing complications of CFTR protein dysfunction and this has led to a steady improvement in survival of CF patients. However, the landscape of CF care has changed substantially over the last decade with the discovery of CFTR modulators that aim to increase or potentially restore the function of the disease-causing CFTR protein. This narrative review summarizes the development of CFTR therapies so far with emphasis on tezacaftor/ivacaftor combination therapy. We have also summarized the Phase II results of triple combination therapy which promises an effective CFTR modulator therapy for more than 90% of CF patients.

Hidden morbidity: The results of a collaborative community chronic obstructive pulmonary disease screening initiative.

Chronic obstructive pulmonary disease (COPD) often goes unrecognised resulting in people living with the disease without a diagnosis. We investigated the characteristics, symptom burden and flow of participants in a community COPD screening initiative. Screening was undertaken during four events over 2-weeks. Participants completed symptom questionnaires and FEV-1/FEV-6 measurement. Patients with FEV-1 <80% predicted or FEV-1 ≥ 80% predicted and FEV-1/FEV-6 <0.72 were considered 'screen-positive' and invited to attend a 1-stop diagnostic clinic. Two hundred and fifty-seven individuals participated (mean ± SD age 58 ± 16, 24% current smokers). Seventy-seven were screen-positive with 27 ultimately attending a 1-stop clinic and 18 having confirmed COPD. The CAT score of participants with COPD was 19.3 ± 11.4. Two-thirds had moderate airflow obstruction on spirometry. The diagnosis rate in this screening initiative was comparable to trials of systematic case finding. Further research is required to explore the broader clinical impact of COPD screening.

Travel with CPAP machines: how frequent and what are the problems?

BACKGROUND: Obstructive sleep apnoea syndrome is a common condition for which continuous positive airways pressure (CPAP) is the standard treatment. The condition affects a population of which a substantial proportion will be travelling. METHODS: We use a questionnaire survey of CPAP users to gain understanding regarding the behaviours, attitudes and problems surrounding travel with CPAP machines during travel and while abroad. All CPAP patients on our database at a UK district general hospital reviewed over a period of 4 years were sent a postal questionnaire. RESULTS: A response rate of 53% was achieved giving data on 588 trips. In the last 2 years, 63.7% of respondents had travelled; reasons for not travelling were CPAP related in only five cases. Travellers took their CPAP machines on 81% of trips. A similar proportion of patients took their CPAP machines regardless of the mode of travel, destination or length of holiday. Problems with checking in the CPAP machine were encountered in 4% of trips, all as part of air travel. Just over a third of patients faced problems either with the power cord, adapter or transport of the CPAP machine. Of those taking overnight flights, half did not sleep and none used their CPAP machines in flight. CPAP usage while away did not differ to usage at home. CONCLUSIONS: This is the first report to describe in some detail CPAP machine use and associated problems in travel and while away. The data may aid the targeting of brief interventions in CPAP clinics as well as helping to standardize the process of check-in in order to help travellers with CPAP machines.

Ivacaftor and symptoms of extra-oesophageal reflux in patients with cystic fibrosis and G551D mutation.

BACKGROUND: Extra-oesophageal reflux (EOR) may lead to microaspiration in patients with cystic fibrosis (CF), a probable cause of deteriorating lung function. Successful clinical trials of ivacaftor highlight opportunities to understand EOR in a real world study. METHODS: Data from 12 patients with CF and the G551D mutation prescribed ivacaftor (150mg bd) was collected at baseline, 6, 26 and 52weeks. The changes in symptoms of EOR were assessed by questionnaire (reflux symptom index (RSI) and Hull airway reflux questionnaire (HARQ)). RESULTS: Six patients presented EOR at baseline (RSI >13; median 13; range 2-29) and 5 presented airway reflux (HARQ >13; median 12; range 3 to 33). Treatment with ivacaftor was associated with a significant reduction of EOR symptoms (P<0∙04 versus baseline) denoted by the reflux symptom index and Hull airway reflux questionnaire. CONCLUSION: Ivacaftor treatment was beneficial for patients with symptoms of EOR, thought to be a precursor to microaspiration.

The diagnostic yield of CTPA: pulmonary embolism, alternative diagnoses and incidental findings.

AIMS: In this retrospective study we assess the diagnostic yield of computed tomography pulmonary angiogram (CTPA) and the incidence of alterative and incidental diagnoses. METHODS: The results of all CTPA scans performed in our trust over a period of 18 months were reviewed and all diagnoses noted. Data collected was descriptively analysed. RESULTS: A total of 1138 scans were performed (56.5% men, mean age 59 years). A diagnosis of pulmonary embolism (PE) was made in 20.2%, an alternative aetiology for presenting symptoms in 26.4% and incidental findings in 19.5%. The commonest alternative diagnosis was pneumonia (9.5%). CONCLUSIONS: Significant numbers of CTPA yield unexpected findings, which may provide an explanation for the clinical presentation. Furthermore substantial numbers of incidental pathologies are also diagnosed which may lead to inappropriate resource utilization and increased patient anxiety.

Defining Chronic Cough: A Systematic Review of the Epidemiological Literature.

PURPOSE: Recent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics. METHODS: A systematic review was conducted for epidemiological surveys that reported the prevalence of chronic cough in general adult populations during the years 1980 to 2013. A literature search was performed on Pubmed and Embase without language restriction. Epidemiological definitions for chronic cough were classified according to their components, such as cutoff duration. Meta-analyses were performed for the male-to-female ratio of chronic cough prevalence to explore operational characteristics of epidemiological definitions. RESULTS: A total of 70 studies were included in the systematic review. The most common epidemiological definition was identified as 'cough ≥3 months' duration without specification of phlegm (n=50); however, it conflicted with the cutoff duration in current clinical guidelines (cough ≥8 weeks). Meta-analyses were performed for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition. The pooled male-to-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I²=96%, P<0.001), which was in contrast to clinical observations of female predominance from specialist clinics. Subgroup analyses did not reverse the ratio or reduce the heterogeneity. CONCLUSIONS: This study identified major issues in defining chronic cough in future epidemiological studies. The conflict between epidemiological and clinical diagnostic criteria needs to be resolved. The unexpected difference in the gender predominance between the community and clinics warrants further studies. Clinical validation of the existing definition is required.

Patient experience surrounding bronchoscopy.

Fiberoptic bronchoscopy (FOB) is a commonly performed procedure in thoracic medicine associated with significant discomfort, which greatly impacts patient satisfaction with the procedure. The UK DoH and BTS stress the benefits of collecting and reviewing patient experiences of a service and how this information should shape service provision. In this current study we assess a number of tolerance and satisfaction related factors in 108 consecutive patients undergoing FOB. We demonstrate a highly significant relationship between patient reported comfort and complete amnesia of FOB. We fail to demonstrate a relationship between patient reported comfort during FOB and the bronchoscopist's assessment of tolerance. We also suggest a relationship between poorer patient reported comfort and a lower WHO performance status. The identification of factors associated with satisfaction with FOB will allow creation of strategies to improve patient experience and lead to better outcomes.