Dear Editor,

We would agree with much of the content of the interesting letter from Doctors Koh and Kwon, particularly the details of M.avium complex infection and the use of CT scans in making the diagnosis.[1] We have also had experience of bronchoscopy and biopsy being necessary to make the diagnosis in some cases with suggestive radiology. The one point on which we disagree is the value of routine annual screening of sputum for AFB, and our practice of sending three samples in all patients with a deterioration in their clinical condition which is not explained or not reversed by usual treatment. The value of this practice will require a large prospective study with cost benefit analysis, and attention paid to false negative results.

However, we would argue in favour of this approach for the following reasons. Most patients have a CT scan when bronchiectasis is first suspected. Our study[2] has shown that these patients in the future may (rarely) contract NTM infection which adversely affects their condition. As Doctors Koh and Kwon state this may be insidious and go unsuspected for long periods. In our study[2] most patients with infection (rather than colonisation) had heavy bacterial load (smear positive), which would make it likely that routine screening would detect the patient. Repeat CT scans in all cases that might raise suspicion of NTM is impractical. Lastly, about 50% of cases with diffuse bronchiectasis remain idiopathic even after full investigation[3], and our understanding of NTM pathogenesis is just begining to increase. The data produced from closely studying NTM in our population of bronchiectatic patients may provide useful information in the future.

R.Wilson, M. Wickremasinghe, L.J. Ozerovitch, G. Davies, T. Wodehouse, M.V. Chadwick, S. Abdallah, P. Shah

References

(1). Hollings NP, Wells AU, Wilson R, Hansell DM Comparative appearances of non-tuberculosis mycobacteria species: a CT study Eur Radiol 2002; 12: 2211-7.

(2). Wickremasinghe M, Ozerovitch LJ, Davies G et al Non-tuberculous mycobacteria in patients with bronchiectasis Thorax 2005: 60: 1045-1051.

(3). Pasteur MC, Helliwell SM, Houghton SJ et al An investigation into causative factors in patients with bronchiectasis Am J Respir Crit Care Med 2000; 162: 1277-1284.

Dear Editor,

We read with great interest the paper by Wickremasinghe et al. on the prevalence of nontuberculous mycobacteria (NTM) in patients with bronchiectasis.[1] They showed that the prevalence of NTM was uncommon (only 2%) both in 50 newly referred patients and 50 follow up patients. However, the authors stated in the Discussion that it is now our practice to screen our patients routinely once a year because a large number of NTM isolates (28%) were detected by routine surveillance in their retrospective analysis of 71 patients with NTM sputum isolates.[1]

NTM pulmonary infection associated with bronchiectasis is increasing worldwide.[2] However, should routine periodic screening for NTM infection be necessary for all adult patients with bronchiectasis? Is sputum culture a sufficiently sensitive method to exclude active NTM infection? Are negative sputum studies sufficient to dissuade one from the diagnosis of active NTM infection?

Bronchiectasis, in general, can manifest in one of two forms: as a local or focal obstructive process of a lobe or segment of a lung or as a diffuse process involving most of the lungs.[3] In patients with diffuse bronchiectasis, the disease is more likely to be associated with specific causes, such as infection (NTM infection, Aspergillus infection), congenital conditions (primary ciliary dyskinesia, cystic fibrosis), or immunodeficiency.[3]

High-resolution computed tomography (HRCT) has proven to be a reliable and noninvasive method for the diagnosis of bronchiectasis. The pattern and distribution of abnormalities revealed by HRCT are influenced by the underlying cause of bronchiectasis. Multiple small nodules (and sometimes cavity or cavities) combined with diffuse (or widespread) bronchiectasis are reported to be the typical HRCT findings of NTM pulmonary infection associated with bronchiectasis,[4-6] which was also suggested by Wickremasinghe et al.[1] In patients with these characteristic HRCT findings, 34-50% of patients have active NTM pulmonary infection, especially M. avium complex infection.[4,6] These abnormalities are usually confined to, or most severe in, the right middle lobe and the lingular segment of the left upper lobe in NTM pulmonary infection. Therefore, this presentation is now referred to as ¡°nodular bronchiectatic disease.[2] Multiple small nodules around ecstatic bronchi on HRCT scan have been reported to represent peribronchial granuloma and caseous material.[4,5]

Diagnosis of this type of NTM pulmonary infection is often delayed; this is because symptoms are mild, and excretion of NTM in sputum is intermittent with few colonies retrievable in culture. Therefore, many patients require bronchoscopy or lung biopsy for diagnosis of NTM pulmonary disease.[7]

Therefore, in clinical practice, HRCT scans should be performed in patients with suspected bronchiectasis. NTM pulmonary infection could be suspected in selected patients who have multiple pulmonary nodules combined with diffuse bronchiectasis on HRCT scans. Multiple sputum specimens should be examined in these patients. However, the poor sensitivity of sputum cultures suggests that in that situation where multiple sputum cultures are nondiagnostic, bronchoscopy should be performed to adequately exclude or diagnose NTM pulmonary disease. We consider that there is no clear evidence to support the routine surveillance for NTM infection in all adult patients with bronchiectasis.

References

1. Wickremasinghe M, Ozerovitch LJ, Davies G, et al. Non-tuberculous mycobacteria in patients with bronchiectasis. Thorax 2005;60:1045-51.

2. American Thoracic Society. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med 1997;156:S1-25.

3. Barker AF. Bronchiectasis. N Engl J Med 2002;346:1383-93.

4. Tanaka E, Amitani R, Niimi A, et al. Yield of computed tomography and bronchoscopy for the diagnosis of Mycobacterium avium complex pulmonary disease. Am J Respir Crit Care Med 1997;155:2041-6.

5. Jeong YJ, Lee KS, Koh WJ, et al. Nontuberculous mycobacterial pulmonary infection in immunocompetent patients: comparison of thin- section CT and histopathologic findings. Radiology 2004;231:880-6.

6. Koh WJ, Lee KS, Kwon OJ, et al. Bilateral bronchiectasis and bronchiolitis at thin-section CT: diagnostic implications in nontuberculous mycobacterial pulmonary infection. Radiology 2005;235:282-8.

7. Huang JH, Kao PN, Adi V, et al. Mycobacterium avium-intracellulare pulmonary infection in HIV-negative patients without preexisting lung disease: diagnostic and management limitations. Chest 1999;115:1033-40.

Dear Editor

I read with interest this article by Sharafkhaneh et al. wherein the role of lung volume reduction surgery (LVRS) in improving expiratory flow limitation by decreasing thoracic gas compression, is indicated

Apart from the obvious benefits for emphysema patients shown in this report, it is important to highlight the other significant beneficial roles of LVRS. The procedure is now considered as an alternative or a bridge to lung transplantation in many candidates with end stage disease who are unable to undergo transplantation owing to limitations regarding age, comorbidity, limited availability of organs and cost [1]. Furthermore LVRS is now considered as an important player in the approach towards lung cancer in advanced emphysema patients [2].

A significant proportion of serious emphysema patients have a long- standing history of smoking. It is noteworthy to rule out other smoking related complications like myocardial ischemia (that may be masked in its signs and symptoms owing to the preexisting exertional ventilatory impairment), which may add to the perioperative mortality of LVRS, further undermining the procedure [3].

Advanced emphysema is a serious morbidity with definitive compromise of ventilatory excursion along with embargos on overall quality of life. Conservative management has been established to offer little as regards halting the disease process or yielding patient physical or mental relief from the progressive burden of the pathology. Ever since the proposition of concept of surgical resection of parts of emphysematous lungs (leading to expansion of remaining lung, thereby increasing elastic recoil and restoring the outwards forces on bronchioles, yielding airflow restoration), an array of clinical trials have been undertaken that demonstrate superiority of LVRS over optimal medical therapy [4]. Trials are somewhat unanimous in proving efficacy of LVRS in improving dyspnea, exercise capacity, physical functioning and patient’s subjective appraisal of the quality of life, particularly pronounced in a selective subset of patients with heterogeneous, upper lobe, smoking related, centrilobular emphysema [5-8].

However, the overall acceptance of LVRS continues to be limited universally owing to paucity of survival benefit and long-term results. Before suspicion settles around these fundamental questions regarding LVRS, hesitance is likely to prevail as regards subjecting patients globally to this serious and expensive procedure.

Over time, understanding of the pathophysiology, operative techniques, risks and benefits, and selection criteria has improved markedly, primarily owing to the multitudes of patients who have undergone LVRS. A restraint on the technique now would deter both the scientific aptitude of health care providers and the potential benefit achievable from the procedure for subjects undergoing it. Emphysema is a chronic debilitating disease. Thousands die every year over the world owing to its end stage. Many more continue to suffer owing to its advanced stage. Such is the physical impairment and diminishment of their life quality, that they would undergo LVRS for symptomatic relief even though it does not extend their life.

The principle of medical therapeutics has never been to increase life span, but merely to better the health related aspect of life. An alteration in the eventual course of Nature cannot be aspired to by physician. Surgery cannot alter the pathological basis of continuing destruction of lung tissue, and therefore not extend survival. Owing to its nature, LVRS, would, however, restore the pulmonary function to a degree that would permit a somewhat normal appreciation of life in these often terminally ill patients. Considering the known benefits of LVRS in this regard and the high number of patients who could potentially advantage, it is indeed questionable to impose financial restrictions and deny access to the procedure to these chronically ailing health care seekers.

References

1. Demertzis S, Wilkens H, Lindenmeir M, et al. Lung volume reduction surgery for severe emphysema. J Cardiovasc Surg (Torino) 1998; 39:843-847.

2. DeMeester SR, Patterson GA, Sundaresan RS, et al. Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema. J Thorac Cardiovasc Surg 1998; 115:681-688.

3. Thurnheer R, Muntwyler J, Stammberger U, et al. Coronary artery disease in patients undergoing lung volume reduction surgery for emphysema. Chest 1997; 112:122-128.

4. Berger RL, Wood KA, Cabral HJ, et al. Lung volume reduction surgery : a meta-analysis of randomized clinical trials. Treat Respir Med 2005; 4:201-209.

5. Bloch KE, Georgescu CL, Russi EW, et al. Gain and subsequent loss of lung function after lung volume reduction surgery in cases of severe emphysema with different morphologic patterns. J Thorac Cardiovasc Surg. 2002; 123:845-854.

6. Iwasaki A, Shirakusa T. Long-term outcomes and possibility of LVRS. Nippon Rinsho 2003; 61:2200-2204.

7. Teschler H, Thompson AB, Stamatis G. Short- and long-term functional results after lung volume reduction surgery for severe emphysema. Eur Respir J 1999; 13:1170-1176.

8. Sugi K, Kaneda Y, Murakami T, et al. The outcome of volume reduction surgery according to the underlying type of emphysema. Surg Today 2001; 31:580-585.

Dear Editor

We have read with great interest, Soler-Catauna and colleagues [1] article that examined, in an impressive prospective study with five years follow-up, factors predicting poor prognosis and mortality in patients with severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Their findings are complimentary with the current available literature in identifying that older age, arterial carbon dioxide tension and acute exacerbations were independent predictors of mortality in their cohort group.

We have concerns however regarding both their analyses and conclusions. Firstly several studies [2,3,4] have given advice on the limitations of dichotomizing continuous predictors as they come at a cost, “as explanatory variables could be seriously misleading, both in respect of which variables are significant in the model, and perhaps to also with respect to the overall predictive ability” [2]. Soler-Cataluna and colleagues state in their “multivariate model the frequency of acute exacerbations, age and Charlson index were analysed as categorical variables” [1].

Secondly, and perhaps more importantly, the authors have reported older age (clearly a non-modifiable factor) as a predictor of death. They do not state whether they believe this to be old age per se or an age- related potentially modifiable variable. Have the authors collected data on social support, physical disability, depression, quality of life and any palliative care their patients may have received during the follow-up period? These variables may have some implication on mortality in this exclusively male COPD patient cohort. Our own group has recently published data on one-year mortality following hospitalisation for AECOPD in a slightly older subject group (mean age 73 years vs. 71 years in the Soler- Cataluna study) and with worse baseline spirometry (mean percentage predicted FEV1 of 39%). In our study age was not a mortality predictor on either univariate or multivariate analysis. Quality of life, level of disability, severity of depression, readmission, use of LTOT and duration of original admission (all of which are arguably related to age), were all univariate predictors of 12-month mortality, with only quality of life score remaining a significant predictor on multivariate analysis.

We wonder whether the inclusion of age-related variables in Soler- Cataluna’s analysis together with the use of age as a continuous variable might have resulted in qualitatively or quantitatively different conclusions regarding the effect of age on prognosis. However the inclusion of duration of original admission and of frequency of readmission in our own list of predictors [5] would support Soler Cataluna’s suggestion that severe AECOPD could have adverse impact on longer term mortality.

References

1.Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-931.

2.Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression a bad idea. Statist Med (in press) – published on line.

3.Cohen J. The cost of dichotomization. Applied psychological Measurement 1983;7:249-253.

4.Irwin JR, McClelland GH. Negative consequences of dichotomizing continuous predictor variables. Journal of Marketing Research 2003;40:366- 371.

5.Yohannes AM, Baldwin RC, Connolly MJ. Predictors of 1-year mortality in patients discharged from hospital following acute exacerbation of chronic obstructive pulmonary disease. Age Ageing 2005;34:491-496.