eLetters

65 e-Letters

published between 2016 and 2019

  • Macrolides and Mycobacterium abscessus - time for a rethink?

    Sir

    We read with interest the latest BTS guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD).1
    Of particular interest was the section relating to the treatment of Mycobacterium abscessus –pulmonary disease. The evidence for the treatment regimes remains poor (Grade D) and within paediatric population the experience of treatment strategies is based on both adult guidelines and clinical expertise. Questions remain about the rationale for the use of macrolides in organisms with inducible resistance. Table 8 in the article recommends the use of oral macrolides during both induction and continuation phase even if inducible macrolide resistance has been demonstrated in vitro. By definition, M. abscessus abscessus strains will possess a functional erm(41) gene, 2 and therefore we feel use of this drug may be inappropriate for this subspecies.

    Azithromycin is a bacteriostatic antibiotic, with intracellular penetration superior to that of the aminoglycosides. 3 M. abscessus complex can thrive within the intracellular environment. 4 Given the exposure of intracellular M. abscessus abscessus to a bacteriostatic agent we suggest this may induce not only resistance but also quiescence within the bacterium and therefore the bactericidal action of aminoglycosides would be significantly impaired given the lack of active protein synthesis. This quiescent state is likely given the difficulty in isolating this organism whilst the...

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  • Inaccuracy regarding Inhaled Corticosteroid equivalence

    While I agree this paper draws out most of the important issues related to the NICE guideline, I would like to point out that there are inaccuracies regarding the statements and table related to 'dose equivalences' in the GINA document.
    In fact reference to equivalence in your article is explicitly contradicted by the statement immediately below GINA table 3-6, which states that 'this is not a table of equivalence, but of estimated clinical comparability'. (1)
    Furthermore the GINA table also takes into account the potential for side-effects. For example, BDP HFA causes more adrenal suppression than FP HFA at the same dose. (2)
    Of course this is going to get even more complicated with the number of generics now available, as they cannot be assumed to be equivalent to the original product, due to the impact of the inhaler device and additives.

    (1) www.ginasthma.org
    (2) Fowler, S. J., Orr, L. C., Wilson, A. M., Sims, E. J. and Lipworth, B. J. (2001), Dose-response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate. British Journal of Clinical Pharmacology, 52: 93-95. doi:10.1046/j.0306-5251.2001.bjcp.1399.x

  • Opioids for the palliation of breathlessness Cochrane review: additional analyses yield same conclusions

    We thank Associate Professor Magnus Ekström et al for their research letter regarding our Cochrane Review: Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness (1,2). We also acknowledge that following the publication of their letter in Thorax, feedback was provided through the appropriate mechanism to the Cochrane Review Group (2). We have published a detailed response to their comments in the feedback section of our review, however, given the seriousness of the criticisms published in Thorax, we think it is important that our response also sit alongside their Thorax letter.

    We acknowledge the statistical difficulties in the interpretation and summation of the complex data on opioids for breathlessness. One such issue is the inclusion of crossover studies in a meta-analysis, however, a crossover design is an appropriate way to assess short term interventions, particularly when patient recruitment may be challenging. The Cochrane Handbook outlines several methods to incorporate crossover data into meta-analyses (3). In using the data as if it was a parallel study, the limitations should be acknowledged, in that it can give rise to a unit of analysis error whereby confidence intervals may be wide, and the overall effect is under-estimated. An alternative method is to calculate correlation co-efficients (which describe the ratio of between-patient standard deviation with the within patient variation) to impute...

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  • Modernising scientific careers in the NHS: capacity building to improve training in pulmonary physiology and the interpretation of lung function tests.

    We read with interest the timely editorial by Gerrard Phillips (1), concerning the importance of providing physiological training to trainee respiratory physicians. This reviewed a French study indicating that trainees who had received an internship in a respiratory lab were substantially better at diagnosing respiratory abnormalities compared with trainees without such training. (2) Dr Phillips made a persuasive, “essential” case for an integrated understanding of respiratory physiology/pathophysiology, lung function testing and interpretation in clinical trainees.

    We strongly agree and also argue that the problem is the recognition of the importance of physiology in general, across the specialist service. We are involved in work that aims to build physiologist numbers, leadership and lab capacity, and feel this could lead to improved training for trainee doctors, as has been shown in the audit of French trainees (2). This would very much benefit from further support from colleagues and hope that the following information helps to make this case.

    In December 2015 the first NHS physiology scientist students of the new national NHS Masters in Respiratory medicine graduated from Newcastle University. This course is part of the national Modernising Scientific Careers (MSC) program in the NHS. The respiratory teaching faculty is consultant led, with delivery in hospital clinical teaching facilities.

    Modernising scientific careers (MSC) is a UK wide initia...

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  • Pleural sclerosis vs pleurodesis

    AMENDED

    Dear Sir,
    In this comprehensive article the authors state that "recurrence prevention involves an attempt at pleurodesis
    ( permanent apposition of the visceral and parietal pleura to seal the pleural space )"
    This is a simple and convincing explanation for any young male suffering persistent or recurrent pneumothorax (or indeed, a patient suffering symptomatic malignant pleural effusion ).
    The histological changes after "pleurodesis" have been widely and clearly described in the literature and universally accepted. ie. fibrin deposition, collagen formation , fibrosis +/- some adhesions.
    However the medical literature seems devoid of descriptions of ablation of the oleural cavity following "successful pleurodesis", at subsequent thoracotomy or post mortem despite the enormous number of such procedures performed since the 1930s.
    This must raise the possibility that such ablation does not occur and that the "clinical success" of the procedure results from the histological changes which are described.
    Are the authors aware of any evidence to support ablation/obliteration of the pleural cavity following this procedure ? Perhaps pleurosclerosis may be a more accurate term

  • The impact of CT screening on the motivation of smoking cessation: A double-edged sword?

    Recently, Kate Brain and colleagues1 reported in the Thorax a randomized controlled trial concerning the favorable effect of CT lung cancer screening on the smoking cessation motivation. The study proved that implementation of a lung cancer screening program offered opportunities of smoking cessation for high risk smokers. Furthermore, this trial suggested that CT lung screening should be integrated into the smoking cessation interventions.
    Although inspiring, the study was not specifically designed to test the effect of lung screening on smokers who received negative screening results. Lacking the comparison between negative and positive ones, we should be cautious in drawing the final conclusion with the findings only from those with positive results of CT scan.
    As we all known, results of CT screening include three categories, namely positive, negative and indeterminate. There has been increasing evidence suggesting that CT lung screening may offer a ‘license to smoke’ for active smokers who have negative results2. For those with indeterminate results, the trend towards increased smoking cessation was not significant though3. In fact, a large number of heavy smokers have no sign of lung cancer in the CT scan in clinical practice, which might make these smokers feel more comfortable to continue smoking. Thus, more attention should be paid to those without positive scanning results. there are several demographic predictors of increased likelihood and motivatio...

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  • Lung cancer screening needs smoking cessation programme

    A quit rate of 21% in controls and 24% in screened persons show that CT screening is a poor motivation to quit. The authors emphasize that the quit rate was 30% in patients with a positive result on CT who needed additional clinical investigation, however, the quit rate was only 15% in persons receiving a negative CT result. This shows that CT screening lowers the motivation to quit if a negative result (expected for the majority) nourishes misperceptions. Zeliadt et al. ( JAMA Intern Med 2015; 175:1530-7) found that in 49% these beliefs were reinforced and potentially exacerbated by screening and lowered the motivation to participate in smoking cessation programs. Therefore CT screening for lung cancer without accompanying smoking cessation program could be harmful.

  • Intensive or longer?

    We read with great interest the article by Wright et al (1) published recently on the Thorax. We congratulate the authors for the study that focused on an important issue, an optimal dose of mobilization in critically ill patients. This is a very well designed clinical trial that allows us to delve deeper into discussions about training load variables applied to critical patients.
    The authors named the main study training load variable of intensity. However we note that the duration of the program was the main difference between the groups and not the intensity. This is, because duration is the time period for a specific activity, while the intensity is relative to the rate of energy expenditure required to perform the activity (aerobic activity) or the magnitude of the force exerted during the resistance exercise (2).
    It was unclear how muscle strength training progressed and there was no measure of energy expenditure (even if indirectly with accelerometers or perceived exertion scales), so we can not clearly state that there was a difference in the intensity of the groups, even though they had a longer duration for the intervention group (3). It is well known that in healthy subjects, shorter duration and shorter intervals may have substantially higher energy expenditure and may affect the metabolic pathways differently (4). A reality that still deserves more attention in intensive care mobilization studies.

    References

    1. Wright SE, Thomas K, Wa...

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  • Changing the way we diagnose UIP: it’s all about probabilities

    I read with great interest the article “The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia”, by Brownell and colleagues [1]. The study has great methodological strength, and I applaud the authors for such an elegant work. But what really caught my attention was the clear use of pre-test probability and likelihood ratio to establish the diagnosis of usual interstitial pneumonia (UIP) in patients with suspected UIP. I believe this article should change the way we care for those patients.

    The study included patients with “possible UIP" and “inconsistent with UIP” patterns on high-resolution computed tomography (HRCT) of the chest. Those patients represent a diagnostic dilemma we commonly face in interstitial lung diseases clinical practice. Three different radiologists (two in the derivation and one in the validation cohort) reviewed the HRCT scans, and most importantly: they were blinded to clinical information and pathology results. All patients had the reference standard surgical lung biopsy, which were prospectively evaluated by expert pathologists.

    The likelihood ratio for male patients, with ≥ 60 years-old, and possible UIP with traction bronchiectasis score ≥ 4 was as high as 47 in the derivation cohort. Since likelihood ratios are a ratio of two likelihoods (the likelihood of a test results in disease / the likelihood of the same test result in no disease [2]), the further away from on...

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  • MRI is promising but not yet ready for routine use

    Magnetic resonance imaging (MRI) of the lung is an exciting field that is currently undergoing a period of rapid advancement. With its ability to measure lung function as well as structure, MRI stands to greatly improve our understanding of cystic fibrosis (CF) pathophysiology in children. However, there are still a number of significant hurdles to overcome if MRI is to become a tool for routine monitoring of paediatric CF lung disease.

    Compared to other commonly used modalities such as computed tomography (CT), spirometry, and multiple breath washout (MBW), MRI is considerably more expensive and, due to high demand, generally has long wait times for access. In addition, the cost of Helium for inhalation as a contrast agent is substantial, and due to diminishing reserves, access is likely to be more problematic in the future. The use of hyperpolarised gas requires expensive equipment that is not available in all centres, such as specially tuned radiofrequency coils and a gas hyperpolariser, as well as the expertise to run them [1]. The significant cost to set up and maintain such a system presents a huge barrier to entry for many CF centres, compared to the nearly universal presence of CT and lung function testing facilities.

    Standardisation of MRI between centres is challenging. Many sequences are protected under intellectual property law resulting in vendor-specific protocols, hampering comparisons between platforms [2]. Magnetic field inhomogeneity can lea...

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