Non-tuberculous mycobacterial pulmonary disease (NTM-PD): Epidemiology, diagnosis and multidisciplinary management.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management.

Demystifying Dry Powder Inhaler Resistance with Relevance to Optimal Patient Care.

The selection of an inhaler device is a key component of respiratory disease management. However, there is a lack of clarity surrounding inhaler resistance and how it impacts inhaler selection. The most common inhaler types are dry powder inhalers (DPIs) that have internal resistance and pressurised metered dose inhalers (pMDIs) that use propellants to deliver the drug dose to the airways. Inhaler resistance varies across the DPIs available on the market, depending largely on the design geometry of the device but also partially on formulation parameters. Factors influencing inhaler choice include measures such as flow rate or pressure drop as well as inhaler technique and patient preference, both of which can lead to improved adherence and outcomes. For optimal disease outcomes, device selection should be individualised, inhaler technique optimised and patient preference considered. By addressing the common clinically relevant questions, this paper aims to demystify how DPI resistance should guide the selection of the right device for the right patient.

Selection of the right inhaler is important to ensure that patients with respiratory diseases get the most benefit from their treatment. Dry powder inhalers and pressurised metered dose inhalers are the most common inhaler types. Pressurised metered dose inhalers use propellants to deliver the drug to the lungs. In contrast, dry powder inhalers deliver the drug to the lungs by having internal resistance. This restricts the flow of air through the inhaler. As the patient inhales through the inhaler, the resistance against the air flow generates the power to separate the drug molecules and carry them to the lungs. While there are many factors to be considered for inhaler selection, there is often confusion around how resistance should guide selection of inhaler. With low-resistance devices, patients must inhale faster to generate the power to separate the drug molecules, which may be difficult in patients with poor lung function. With high-resistance devices, patients do not need to inhale as fast to separate the drug, and most patients can effectively use the inhaler. This article addresses the common clinically relevant questions to clarify how the internal resistance of the inhaler should be used to help guide the selection of the right device for the right patient.

Healthcare costs associated with short-acting ß2-agonists in asthma: observational UK SABINA study.

BACKGROUND: Poor asthma control is associated with high short-acting ß2-agonist (SABA) use. AIM: To assess asthma-related healthcare resource utilisation (HCRU) and medication costs associated with high versus low SABA prescriptions in the UK. DESIGN & SETTING: Analysis of SABINA I (SABA use IN Asthma I), a retrospective longitudinal study using UK electronic health records (Clinical Practice Research Datalink GOLD 2008-2019 and Hospital Episode Statistics database). METHOD: Eligible patients were ≥12 years old with SABA prescriptions in the past year. SABA prescriptions (number of canisters per year) were defined as high (≥3) or low (1-2). Association of SABA prescriptions with HCRU was assessed by negative binominal model adjusted for covariates. The UK unit costs from the NHS were applied to estimate total healthcare costs (2020). Medication costs were based on the annual average number of canisters per year per patient. RESULTS: Overall, 186 061 patients with SABA prescriptions were included, of whom 51% were prescribed high SABA. Total annual average costs (HCRU and medication) were 52% higher in the high SABA group versus the low SABA group (£2 256 091 per 1000 patients/year versus £1 480 640 per 1000 patients/year). Medication costs accounted for the majority of asthma-related costs. Across both groups, most HCRU costs were for non-exacerbation-related primary care or hospital outpatient visits. The annual average HCRU cost difference for high SABA versus low SABA was the greatest for hospitalisations (+230%; £15 521 per 1000 patients/year versus £4697 per 1000 patients/year) and exacerbation-related primary care visits (+162%; £18 770 per 1000 patients/year versus £7160 per 1000 patients/year). Asthma-related HCRU extrapolated to the broader UK asthma population was £108.5 million per year higher with high SABA versus low SABA. CONCLUSION: High SABA versus low SABA prescriptions are associated with higher asthma-related HCRU costs.

Cost-consequence analysis of COPD treatment according to NICE and GOLD recommendations compared with current clinical practice in the UK.

OBJECTIVES: The objective of this study was to model the clinical and economic impact of adapting current clinical practice in the management of patients with chronic obstructive pulmonary disease (COPD) to treatment according to national and international guideline recommendations. DESIGN: Treatment mapping was undertaken to hypothetically redistribute patients from current clinical practice, representing actual prescribing patterns in the UK, to an alternative recommendation-based treatment scenario, representing prescribing in accordance with either National Institute for Health and Care Excellence (NICE) guidance [NG115] or Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 strategy. SETTING: Primary care practices in the UK (1-year time horizon). PARTICIPANTS: Adults with COPD undergoing long-acting inhaler maintenance therapy in the UK (N=1 067,531). INTERVENTIONS: Inhaler maintenance therapy. OUTCOME MEASURES: Costs and clinical outcomes (type of treatment, rates of moderate and/or severe exacerbations, and mild-to-moderate and/or severe pneumonia events) were modelled for the two alternative pathways. RESULTS: Compared with current clinical practice, treating patients according to NICE guidance resulted in an estimated annual reduction in expenditure of £46.9 million, and an estimated annual reduction in expenditure of over £43.7 million when patients were treated according to GOLD 2020 strategy. Total cost savings of up to 8% annually could be achieved by treatment of patients according to either of these recommendations. Cost savings arose from a reduction in the rates of pneumonia, with an associated decrease in costs associated with antibiotic use and hospitalisation. Savings were achieved overall despite a small increase in the rate of exacerbations due to the redistribution of certain patients currently undergoing triple inhaled therapy to therapies not containing inhaled corticosteroids. CONCLUSION: Redistribution of patients with COPD from current clinical practice to treatment according to published recommendations would provide substantial cost savings over the first year.

Adapting Inhaled Medication Practice in COPD and Asthma to Avoid Funding the Tobacco Industry.

The takeover of Vectura, a healthcare company specialising in inhaled medication, by Philip Morris International raises serious ethical concerns. The European Respiratory Society notes that "health professionals will avoid prescribing drugs from any company that enriches the tobacco industry due to the ethical implications". People with chronic obstructive pulmonary disease (COPD) and asthma will also be reluctant to use medications which profit a company that is estimated to kill at least one million people every year. We discuss the practicalities involved in switching people with lung disease to inhaled medications that are not tobacco industry linked. Potential alternative inhaled medications are set out, which are likely to be equally effective for most patients. A consideration of beneficence, non-maleficence, autonomy, and distributive justice demonstrates strong ethical reasons to support switching away from the prescription of tobacco industry linked products.

Ward based inhaler technique service reduces exacerbations of asthma and COPD.

BACKGROUND: The management of asthma and COPD is largely dependent on patients being able to use their inhaled medication correctly, but poor inhaler technique continues to be a recurring theme in studies and clinical practice. This is associated with poor disease control, increased risk of exacerbations and hospital admissions, and so there is a need to redesign services for patients to optimise their medicines use. METHODS: A novel ward-based dedicated inhaler technique service was developed, and pharmacy support workers trained to provide this, focusing on optimising inhaler technique using a checklist and recommending protocol-guided inhaler device switches. Inpatients on adult respiratory wards with a diagnosis of exacerbation of asthma or COPD consented to receive this service, and the impact on exacerbations and hospital admissions were compared in the 6-months before and after the intervention. RESULTS: 266 adults (74 asthma, 188 COPD, and four asthma-COPD overlap) received the inhaler technique service. Six-month exacerbation and hospital admission data were available for 184 subjects. Optimising inhaler technique achieved a significant reduction in the combined asthma and COPD annualised rate of moderate-to-severe exacerbations (Rate Ratio [RR] 0.75, p < 0.05) and annualised rate of hospital admissions (RR 0.57, p < 0.0005). Improvements were also observed in future length of stay (- 1.6 days) and the average cost of admission (-£748). CONCLUSIONS: This novel inhaler technique service produced a significant reduction in the rate of moderate-to-severe exacerbations of asthma and COPD, and a reduction in the rate hospital admissions, length of stay and average cost of admission.

The Perils and Pitfalls of Esophageal Dysmotility in Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux-a prerequisite of aspiration), and pulmonary function in patients with IPF. METHODS: We prospectively recruited 35 patients with IPF (aged 53-75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment. RESULTS: Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux (P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = -0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = -0.478; P = 0.098) and number of proximal events (r = -0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = -0.520; P = 0.039) and inspiratory LESP (r = -0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008). DISCUSSION: We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs.

Consistency of recommendations from clinical practice guidelines for the management of critically ill COVID-19 patients.

BACKGROUND: A significant knowledge gap exists for the management of critically ill patients with coronavirus disease 2019 (COVID-19). This study aimed to systematically investigate the consistency of recommendations from the available clinical practice guidelines (CPGs) to those of the WHO on the management of critically ill COVID-19 patients. METHODS: We examined CPGs and UpToDate point-of-care resources on the management of critically ill COVID-19 patients that had been published as of 30 April 2020 and compared them against the CPG by the WHO. The main outcome was the rate of consistency among CPGs for the management of critically ill COVID-19 patients. Sensitivity analyses were conducted by excluding recommendation statements that were described as insufficient evidence and by excluding single CPGs one at a time. RESULTS: Thirteen reference recommendations derived from the CPG of the WHO were generated using discrete and unambiguous specifications of the population, intervention, and comparison states. Across CPGs, the rate of consistency in direction with the WHO is 7.7%. When insufficient evidence codings were excluded, the rate of consistency increased substantially to 61.5%. The results of a leave-one-out sensitivity analysis suggested that the UpToDate recommendation source could explain the inconsistency. Consistency in direction rates changed by an absolute 23.1% (from 1/13 (7.7%) to 4/13 (30.8%)) if UpToDate was removed. CONCLUSIONS: We observed inconsistencies between some recommendations of the CPGs and those of the WHO. These inconsistencies should best be addressed by consensus among the relevant bodies to avoid confusion in clinical practice while awaiting clinical trials to inform us of the best practice.

Use of corticosteroids in asthma and COPD patients with or without COVID-19.

The potential detrimental effects of steroids on the immune system to fight viral infections had always been a concern for patients on long term steroids in chronic conditions. A recent warning from WHO on systemic corticosteroid use amid COVID-19 raised suspicion among public and healthcare professionals regarding the safety of steroid use during the SARS-CoV-2 pandemic. The corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients and any unsolicited changes in medications use may lead to potentially severe exacerbations and may risk patient lives. This article provides a critical review of clinical evidence and offers a detailed discussion on the safety and efficacy of corticosteroids in asthma and COPD patients, both with and without COVID-19.

Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis.

OBJECTIVES: The acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019). We systematically reviewed mortality in COVID-19 patients with ARDS and the potential role of systemic corticosteroids in COVID-19 patients. METHODS: Electronic databases and country-specific healthcare databases were searched to identify relevant studies/reports. The quality assessment of individual studies was conducted using the Newcastle-Ottawa Scale. Country-specific proportion of individuals with COVID-19 who developed ARDS and reported death were combined in a random-effect meta-analysis to give a pooled mortality estimate of ARDS. RESULTS: The overall pooled mortality estimate among 10,815 ARDS cases in COVID-19 patients was 39% (95% CI: 23-56%). The pooled mortality estimate for China was 69% (95% CI: 67-72%). In Europe, the highest mortality estimate among COVID-19 patients with ARDS was reported in Poland (73%; 95% CI: 58-86%) while Germany had the lowest mortality estimate (13%; 95% CI: 2-29%) among COVID-19 patients with ARDS. The median crude mortality rate of COVID-19 patients with reported corticosteroid use was 28.0% (lower quartile: 13.9%; upper quartile: 53.6%). CONCLUSIONS: The high mortality in COVID-19 associated ARDS necessitates a prompt and aggressive treatment strategy which includes corticosteroids. Most of the studies included no information on the dosing regimen of corticosteroid therapy, however, low-dose corticosteroid therapy or pulse corticosteroid therapy appears to have a beneficial role in the management of severely ill COVID-19 patients.

British Thoracic Society Guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD).

The full guideline for the management of non-tuberculous mycobacterial pulmonary disease is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.

Is the 'blue' colour convention for inhaled reliever medications important? A UK-based survey of healthcare professionals and patients with airways disease.

In many countries, short-acting ß2-agonist inhalers have traditionally been coloured blue. This inhaled therapy has also conventionally been known as a 'reliever' by patients and healthcare professionals (HCPs), in comparison with 'preventer' medications (inhaled steroids). With the rapidly changing market in inhaled therapy for COPD and asthma and growing numbers of devices, there has been some concern that the erosion of traditional colour conventions is leading to patients (and HCPs) becoming confused about the role of different therapies. In order to assess whether there was concern over the perceived changing colour conventions, the UK Inhaler Group carried out a large online survey of patients and HCPs. The aim was to determine how patients and HCPS identify and describe inhaled drugs, and how this might impact on use of medicines and safety. The results of the survey highlighted the importance of the term 'blue inhaler' for patients with only 11.3% never referring to the colour when referring to their inhaler. For HCPs, 95% felt colour conventions were important when referring to reliever medication. In addition, HCPs appear to refer to inhalers mainly by colour when talking to patients. Our conclusions were that the concept of a 'blue inhaler' remains important to patients and healthcare professionals. These results add to the debate about the need to formalise the colour coding of inhaled therapies, in particular using the colour blue for inhalers for rapid relief of symptoms, as this convention may be an important measure and contributor to patient safety. Our survey should provide impetus for all interested parties to discuss and agree a formal industry-wide approach to colour coding of inhaled therapies for the benefit of patients and carers and HCPs.

Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma.

Asthma and chronic obstructive pulmonary disease are both common conditions with an increasing prevalence worldwide. Inhaled therapy for these conditions has a number of advantages over systemic therapy, including reduced side effects and quicker onset of action. The effective use of inhaled therapy is critically dependent upon the nature of the drug-delivery system and the ability of the patient to use the system correctly. There are a wide number of inhaler devices on the market, each with positive and negative aspects. A crucial part of patient care is to ensure that the choice of inhaler device for the individual is an effective therapy. There are a number of interventions that can help with the choice of inhaler device and also improve the ability of the patient to use inhaled therapy. Inhaler technique training needs to be a cornerstone of the care of patients with asthma or chronic obstructive pulmonary disease to ensure optimal therapy.