91 e-Letters

published between 2020 and 2023

  • Underrepresentation of low- and middle-income countries in "Core outcome set for pulmonary rehabilitation of patients with COPD: results of a modified Delphi survey"

    If a core outcome set (COS) to a global burden of disease is to be globally relevant and applicable, methodological efforts to ensure equal representation of low- and middle-income countries (LMICs) and high-income countries (HICs) at all stages of its development are needed (1, 2). This is due to the differences in disease patterns, healthcare resources, culture, and biomedical beliefs, which may influence outcome priorities (3, 4). A case in point is a study by Van Rijssen et al (5), where participants from Europe, the USA, and Asia did not reach the same consensus on the final patient-reported COS for pancreatic cancer, and Asian participants did not reach a consensus on any outcomes included in the final set.

    We read with interest your COS for pulmonary rehabilitation (PR) of patients with COPD in the 2023 September issue of Thorax "(6). We noticed the under-representation of LMICs, especially in Asia and Africa, in your development of the COS. Of the 29 and 27 countries where you recruited participants in the first and second rounds of your Delphi survey, respectively, Asia was represented by only one participant from India, whilst no participant was recruited from Africa. Most participants were from HICs in Europe including the Netherlands, Portugal, United Kingdom, Australia, and Spain.

    This underrepresentation of LMICs is noteworthy given that, firstly, the burden of chronic respiratory diseases (including COPD) is greater in LMICs, both in terms...

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  • Response to "Underrepresentation of low- and middle-income countries"

    We thank Bickton and colleagues for their interest in reading our article and their commentary.
    We recognize the need to have a balanced representation of low- and middle-income countries (LMICs) in core outcome sets (COS), specifically in pulmonary rehabilitation (PR) as resources for measurement instruments may vary globally and the burden of COPD and need for pulmonary rehabilitation in these regions are undeniable.
    According to the World Bank categories (1), we have included some middle-income countries in our study, from south America (Argentina, Brazil, Colombia, Cuba) and from Asia (not only India, but also the Philippines). Nonetheless, as acknowledged in our COS paper (2), the African and Asian continents were underrepresented.
    Although not stated throughout our paper, with the a priori knowledge of the need to include these continents and LMICs, we took some methodological steps to try to ensure their representation. Indeed, we have contacted several professional and patient associations from these regions to help us recruit participants. The Pan African Thoracic Society was contacted directly. Nonetheless, the procedure to contact is a form on a website (https://panafricanthoracic.org/about-us/contact-us), with no other form of contact provided. No response was ever obtained. We congratulate the newly formed PR Working Group, and we look forward to enhancing our communication chan...

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  • Letter to the editors. The effect of vibrotactile PT on patient with positional obstructive sleep apnoea (POSA).

    The systematic review and meta-analysis by Abdullah ALQarni et al. on the effect of positional vibrotactile therapy for positional obstructive sleep apnoea shows that this treatment modality is effective, reducing time in the supine position, severity of obstructive sleep apnoea and daytime sleepiness. (1) It also highlights the lack of patient-centered outcomes beyond daytime sleepiness, which is very important to achieve good adherence to treatment, one of the main limitations of obstructive sleep apnoea treatment to achieve greater health benefits for patients as shown by different clinical trials that have failed to show significant results of continuous airway pressure (CPAP) in the prevention of cardiovascular events in intention-to-treat analyses but did show significant results in patients with good adherence to treatment (2).
    Based on this statement, we would like to refer you to our last publication (3), a RCT, which shows high good compliance rates for the active device (mean value of 85% ± 36.6%, defined as device use for more than 4 hours per night and more than 70% of nights per week), values above the usual ones for CPAP treatment, (generally 40%–50% in the long term)(4,5), from the first day and sustained form over time. Patient ́s satisfaction was high and minor side effects were reported.
    Our previous research showed their efficacy in terms of reduction of Apnoea-Hypopnoea Index, total sleep time in the supine position; improve oxygen saturati...

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  • Potential benefits of long-term pulmonary rehabilitation to preserve exercise capacity in patients with idiopathic pulmonary fibrosis treated with antifibrotic drugs.

    We were interested in the article "Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial" by Kataoka K. et al. [1] The effect of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis (IPF) is a topical theme in this field. We believe that this multicenter randomised controlled trial conducted in Japan will have an enormous impact on the knowledge of pulmonary rehabilitation in patients with IPF.
    The authors conducted a 12-week supervised and home-based unsupervised exercise therapy-based pulmonary rehabilitation for 45 outpatients with IPF treated with antifibrotic drugs. In addition, the patients were followed by a 40-week home-based unsupervised exercise therapy-based maintenance program. The pulmonary rehabilitation resulted in a more significant change (week 52 - Baseline) in endurance time measured by a constant workload test using a bicycle ergometer compared to 43 control patients who received only usual care (mean difference: 187 s [95% CI: 34 to 153]). Although endurance time is a secondary outcome in the authors' study design, this result suggests that IPF patients treated with antifibrotic drugs may benefit from pulmonary rehabilitation as a combination therapy to maintain exercise tolerance.
    In contrast, the authors found no statistically significant between-group differences in the change in 6-minute walking distance (6MWD) (52 weeks - Baseline), the prima...

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  • Reply to Drs Abul-Ainine and Steer re: Aminophylline and the British Asthma Guidelines In Children
    Gary Connett

    Dear Editor

    Drs Abul-Ainine and Steer have provided cogent arguments for the use of a 10mg/kg loading dose of intravenous aminophylline to treat acute asthma in children.[1] Their pharmacokinetic evidence for this dose is supported by Yung et al’s randomised placebo controlled trial using this same loading dose.[2] This study recruited 163 children with severe acute asthma unresponsive to three nebulised doses...

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  • Asthma and obesity. Associations exist, but they may not be in direct causal relationship

    Dear Editor,

    I read with interest the recent publication by Subharta Moitra et al in Thorax.(1) The authors concluded that adult asthmatics have a higher risk of developing obesity than non-asthmatics. An association was found especially in non-atopic asthmatics with longer disease duration and the use of oral corticosteroids (OCS).

    Obesity is the strongest risk factor for sleep apnea, and sleep apnea is associated also with asthma.(2) Obesity has been regarded also as a risk factor for developing asthma,(3) but the reverse association is still not clear. Both asthma and obesity begin often in early childhood, and they may share a common background.(3)

    The relationships between smoking, physical activity, use of OCS and lung function were discussed in the paper. But why would asthma per se increase weight? Obesity may be considered also as a central nervous system disorder. Obesity and sleep apnea are associated with asthma. Short night sleep, sleep deprivation and chronic insomnia are associated with the development of obesity.(4) Studies have also shown an association between anxiety, depressive symptoms and the development of obesity.(4)

    The ECHRS cohort was initiated in 1990. The study was focused on asthma, and unfortunately the original questionnaires did not include questions on sleep, sleep disorders or mental health. Also, no sleep studies or psychological testing were done. This explains the lack of information on anxiety, depres...

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  • Reply to: CFTR dysfunction as a cause for increased epithelial sodium channel function in acute respiratory distress syndrome

    We have read with interest the letter from Dr. Eisenhut in this issue of the Journal and thank him for his comments on our work. The theory regarding reduced Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction in acute respiratory distress syndrome (ARDS) is interesting, though remains speculative at present. While some rationale exists to explain why transmembrane ion channels may be dysregulated in inflammation,1 we did not directly examine CFTR function in our original work.2 To test this hypothesis, direct augmentation of CFTR function during a nasal potential difference reading, or measurement of sweat chloride concentration, or another surrogate measure of CFTR function, would need to additionally be incorporated into our study design. We are not aware of any published studies of directly measured CFTR function in adults with ARDS.


    1. Eisenhut M, Wallace H. Ion channels in inflammation. Pflugers Arch 2011; 461(4): 401-21.
    2. MacSweeney R, Reddy K, Davies JC, et al. Transepithelial nasal potential difference in patients with, and at risk of acute respiratory distress syndrome. Thorax 2021; 76(11): 1099-107.
    3. Davis PB, Del Rio S, Muntz JA, Dieckman L. Sweat chloride concentration in adults with pulmonary diseases. Am Rev Respir Dis 1983; 128(1): 34-7.

  • CFTR dysfunction as a cause for increased epithelial sodium channel function in acute respiratory distress syndrome

    MacSweeney et al. in their recent report of transepithelial nasal potential difference measurements in patients at risk of acute respiratory distress syndrome documented that the amiloride response of nasal respiratory epithelium was significantly greater in patients who progressed to develop ARDS compared to those who did not (1). It was also greater in patients who died with ARDS compared to survivors. This is consistent with an increased epithelial sodium channel function in patients at risk of ARDS and its associated mortality. We previously conducted nasal potential difference measurements in children with and without meningococcal septicemia associated pulmonary edema and controls on a Pediatric Intensive Care Unit (2). We found that the amiloride response was greater in patients with pulmonary edema compared to controls but this effect did not reach statistical significance which may have been due to the small number of patients we could enrol (n=4 with pulmonary edema, n=2 with septicemia without pulmonary edema and 8 controls) (2). Despite this small number of patients we found that the nasal potential response to a low chloride solution in patients with septicemia associated pulmonary edema compared to controls was significantly reduced indicating a concomitant dysfunction of respiratory epithelial chloride channels.
    It is known from in vitro studies that the epithelial sodium channel is inhibited by the Cystic Fibrosis Transmembrane Conductance Regulator (...

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  • Clinical Experience Using LVR for Patients with DMD

    We thank the authors for their contribution of a RCT of boys with DMD (FVC>60%) with the intervention of active LVR (air stacking) twice daily for two years. In our clinical practice, we have introduced LVR to thousands of patients with ventilatory pump failure and over 300 with DMD. Although we have not found LVR to preserve or improve vital capacity (VC), patients with 0 mL of VC can survive for decades using up to continuous noninvasive ventilatory support (CNVS). On the other hand, improvement of maximum insufflation capacity (MIC) is reported to improve significantly with practice of LVR, although this is also not crucial.1 What is certain is that tachypneic hypercapnic patients with shallow breathing associated with supplemental oxygen therapy often cannot normalize their blood gases by NVS settings until the O2 is discontinued and the patient practices LVR aggressively for several weeks to several months. At that point their lungs become more compliant and delivered air volumes can normalize their blood gases.2,3 Also, ventilator “unweanable” patients who practice air stacking via mouth and/or nose pieces are much easier to extubate to mouthpiece and nasal CNVS than patients who have not practiced this technique.3,4 Further, air stacking can improve peak cough flows (PCF), phonation, and time to swallow food.5 While McKim et al. suggested initiation of air stacking for DMD once VC decreases below 80%, we have usually begun once the absolute plateau VC is reached...

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  • Response to “Clinical Experience Using LVR for Patients with DMD”

    We appreciate Dr. Ganapa and colleagues’ letter in response to our randomized controlled trial of lung volume recruitment (LVR) in Duchenne muscular dystrophy (DMD). We wholeheartedly agree that LVR has a critical role in the management of individuals with DMD during acute exacerbations and in individuals with advanced neuromuscular disease, especially in those with respiratory failure. The use of LVR in this context is supported by international clinical care guidelines [1-6] and data which demonstrates improvement in lung function decline and maximum insufflation capacity with routine twice-daily LVR.[7-9]

    In our cohort with relatively preserved lung function (baseline median FVC 84.8%, IQR 73.3, 95.5%), the median age of our group (baseline median 11.5 years, IQR 9.5, 13.5 years) is slightly younger than that described by Dr. Ganapa, in whom routine LVR is initiated. Recent data from the Cooperative International Neuromuscular Research Group’s Duchenne Natural History Study indicates, however, that peak median FVC occurs at age 17.0-17.9 years in those with glucocorticoid exposure for greater than one year, compared to age 12.0-12.9 years in those not treated with glucocorticoids.[10] Eighty-nine percent of our cohort were treated with systemic steroids, which likely explains why many had normal FVC at baseline and why it was challenging to show improvements in the rate of decline of FVC over two years with LVR treatment.

    Despite the clear benefits of L...

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