59 e-Letters

published between 2020 and 2023

  • 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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  • Discrepancy between overall ATE frequency stated in abstract vs main text

    Thank you to the authors for this important and detailed analysis. I write to simply draw attention to a discrepancy, unless I am mistaken, between the ATE frequency rates stated in the abstract and those in the main text.

    Abstract: "The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I2=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I2=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I2=84%; 17 studies; 20 139 patients), respectively".

    Main text: "The weighted frequency of ATE was 4.0% (95%CI 2.0% to 6.5%, I2 =95%; 19 studies; 8249 patients), including myocardial
    infarction/acute coronary syndrome (1.1%, 95%CI 0.2% to 3.0%, I2=96%; 16 studies; 7939 patients), ischaemic stroke (1.6%, 95%CI 1.0% to 2.2%, I2 =93%; 27 studies; 40597 patients) and other ATE (0.9%, 95%CI 0.5% to 1.5%; I2
    =84%; 17 studies; 20139 patients)

  • 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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  • 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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  • Can airways endothelial-epithelial cooperation stop Covid-19’s march to the lung?

    The state-of-the-art-review by Bridges et al. (1) entitled “Respiratory epithelial responses to SARS-CoV-2 in COVID-19” admirably updates current concepts ranging from bedside observations to cell signaling. The authors emphasize epithelial interferon/cytokine defense in upper airways, where infection starts. Advanced Covid-19 is then depicted involving alveolar and capillary injury with uncontrolled leakage of plasma from the pulmonary microcirculation (1).

    The subepithelial microcirculations that carry oxygenized blood to nasal, tracheal, and bronchial mucosae are not mentioned. Yet, infection of these conducting airways causes exudation of plasma proteins with well-known antimicrobial defense capacities. Furthermore, contrasting protein leak at lung injury (1), the airways exudative response reflects well-controlled physiological microvascular-epithelial cooperation (2).

    Minimal size-selectivity at exudation of plasma across endothelial-epithelial barriers.
    Observations in infected airways, allergic disease and mediator challenge demonstrate unfiltered and well-controlled plasma exudation responses in human airways. Lack of size-selectivity means that potent cascade systems (complement, kinin/kallikrein, coagulation) and natural antibodies (IgG,IgM) emerge locally, along with albumin, on engaged airway epithelial sites (3-13). Even cathelicidine, representing antimicrobial peptides, arrives on the affected airway surface exclusively as component of...

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  • Is Telerehabilitation a Realistic Alternative to Centre-based Pulmonary Rehabilitation?

    The benefits of pulmonary rehabilitation for individuals with chronic respiratory diseases are well-documented1, but referral practices and programme completion have remained challenging. This has been exacerbated by the COVID-19 pandemic and shielding practices. Thus, highlighting the usefulness of developing a robust telerehabilitation programme as a substitute for centre-based programmes. The data gained from Cox et al addresses this area and demonstrates clinically meaningful advantages of telerehabilitation and is warmly welcomed. A detailed breakdown of the costs involved between both arms would be very helpful in assessing an overall equivalence of the two arms.

    The CRQ is a validated tool for use in research; however, the use of its dyspnoea domain specifically has been shown to be less reliable in comparative research2. Other tools which may be a useful substitute for this study would be ‘incremental shuttle walking test’3 and ‘St George’s respiratory questionnaire’4.

    The number of participants presenting to community healthcare services, and/or those requiring rescue therapy for a mild exacerbation (e.g., antibiotics and/or a short course of corticosteroids) not requiring presentation to a hospital, during the study and follow-up period, may be useful for further assessment of the equivalence of telerehabilitation versus centre-based programmes.

    This study provides useful data regarding the potential benefits of incorporating telerehabilita...

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  • Response to “Letter to the Editor on Thomsen, et al. by Moolgavkar and Attanoos”

    We agree with Drs. Moolgavkar and Attanoos that our observation of increased risk of asbestosis unaccompanied by increased risk of mesothelioma among motor vehicle mechanics (Thomsen, 2021) is inconsistent with other studies of chrysotile exposed populations. As we discussed in our paper, mesothelioma ascertainment is highly reliable in Denmark and our mesothelioma findings are consistent with previous studies (DeBono, 2021; Garabrant, 2016; Hessel, 2021; Tomasallo, 2018; Van den Borre, 2015). Thus, we believe our findings are reliable. Conversely, the asbestosis findings raise important questions. A diagnosis of asbestosis can only be made when a clinician believes the patient has been exposed to asbestos. Pulmonary fibrosis in a vehicle mechanic might readily be diagnosed as asbestosis if the clinician was aware of the occupational history and possible presence of asbestos in brakes, clutches, gaskets, or other vehicle parts. Since our comparison subjects held jobs that did not involve obvious asbestos exposure, it is less likely that pulmonary fibrosis would be diagnosed as asbestosis in this group. Moolgavkar and Attanoos suggest that our comparison selection could have led to diagnostic bias if the vehicle mechanics and the comparisons did not have equal probabilities of exposure to asbestos from sources other than friction products. We agree - we reported that the abrupt increase in outpatient clinic diagnosed asbestosis beginning in the mid-2000s is consistent with...

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  • Letter To The Editor on Thomsen et al

    Thomsen et al’s. (2021)1 suggestion that “asbestosis occurs at cumulative chrysotile exposure levels where mesotheliomas are rare or none were observed…”.to explain the increased risk of asbestosis in the absence of an increased risk of mesothelioma among vehicle mechanics appears implausible for many reasons:
    a. Scientific literature shows that when there is a risk of asbestosis there is also an increased risk of pleural mesothelioma2;
    b. Cumulative exposures to chrysotile asbestos sustained by career vehicle mechanics are far below the cumulative asbestos exposures traditionally associated with asbestosis (25 fibre/cc-years) as cited by Thomsen et al.1,3;
    c. That chrysotile asbestos, with much shorter biopersistence than amphibole asbestos, is more fibrogenic is biologically implausible, and inconsistent with the studies that show that the degree of lung fibrosis/asbestosis correlates with retained amphibole asbestos content, not chrysotile 3,4.
    d. Fibre counts amongst vehicle mechanics with mesothelioma have been found to be either within control reference limits or show increased commercial amphibole asbestos, unrelated to friction exposures 2.
    e. Animal studies do not report asbestosis or mesothelioma following high-dose inhalation exposures to brake dust with and without added chrysotile 5.
    We consider, as Thomsen et al 1 did, that the most plausible explanation is diagnostic bias based on control selection.
    In Thomsen et al...

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