Dear Editor

We thank Dr Singh for his/her comments on our case report.[1] We agree that LIP is an important differential diagnosis in this case and is associated with pulmonary nodules and pulmonary cysts, although they are usually perivascular.[1-3] Firstly we acknowledge an erratum in the text which was edited and submitted without re-review by the contributing pathologist (AR). Specifically there were numerous small non-necrotising epithelioid granulomata within the lung parenchyma. These were interpreted as possibly representing an immune reconstitution process, either to Mycobacterial infection or even latent sarcoidosis.

Given the limits on the length of the pictorial report we did not discuss this particular aspect but the open lung biopsies showed very mild peribronchial chronic inflammation only, and the histological features of LIP were not present. The phenomena of cystic change occurring in the context of TB is in fact described previously and the point of the case report was to demonstrate this radiological picture in the context of having definitive histology ruling out other pathologies. [4,5]

Another possibility was that this case was smoking related Langerhans cell histocytosis (LCH), which can also cause cystic changes in the lung but importantly the patient had in fact stopped smoking as a result of the admission and therefore the imaging would have been expected to improve rather than deteriorate during the course of treatment. In addition there were no histological features of LCH in the lung biopsies.

In summary we feel that we adequately eliminated other known causes of pulmonary cystic disease seen in HIV disease in this case.[5]

References

1. Singh N. LIP reading is required. Thorax eletters

2. Lynch DA, Travis WD, Muller NL, Galvin JR, Hansell DM, Grenier PA, King TE Jr Idiopathic interstitial pneumonias: CT features. Radiology 2005;236(1):10-21.

3: Ichikawa Y, Kinoshita M, Koga T, Oizumi K, Fujimoto K, Hayabuchi N. Lung cyst formation in lymphocytic interstitial pneumonia: CT features. Journal of Computer Assisted Tomography 1994;18(5):745-8. PMID: 8089323

4: Takemura T, Akiyama O, Yanagawa T, Ikushima S, Ando T, Oritsu M. Pulmonary tuberculosis with unusual cystic change in an immunocompromised host. Pathology International 2000;50(8):672-7. PMID: 10972868

5: Ko KS, Lee KS, Kim Y, Kim SJ, Kwon OJ, Kim JS. Reversible cystic disease associated with pulmonary tuberculosis: radiologic findings. Radiology 1997;204(1):165-9. PMID: 9205240

6) Richardson D, Rubinstein L, Ross E, Rice A, Wright AR, Kon OM, Walsh J. Cystic lung lesions as an immune reconstitution inflammatory syndrome. Thorax 2005;60(10):884

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

The study by Duffy et al,(1) published in the September issue of Thorax, has a number of errors in the design and interpretation of the results.

In the study design; 1- By definition COPD is a condition where FEV1 changes very little, so a study of COPD intervention based on change in FEV1 is not correct. 2- The study was in theory powered to show what amounts to about 30% improvement in FEV1 (baseline FEV1 approx 600mls and expected difference 200mls) between the 2 regimens, which is unlikely to occur in COPD patients. So in a way the results were already known prior to start of the study. 3- By leaving the decision of stopping treatment to individual consultants rather than using a fixed protocol makes the results prone to bias. 4- As this a study of acute exacerbation, it should have been analysed at the end of first 12 hours, as any changes seen later are not ‘acute’ but simply reflect differences in practice.

In the results section; 1- The duration of therapy reflects the rate of clinical improvement between active drug and placebo, as the IV therapy would have been stopped once clinical improvement was seen. This difference is almost statistically significant, which has not been elaborated. 2- While all patients were assessed within a 4 hours of admission. But during an acute illness the symptom scores and other ‘baseline’ parameters are likely to have altered in 4 hours. Ideally these should have been recorded prior to receiving any treatment. 3- The calculations and graphs are based on 5 days of therapy where it is clear that on days 4/5 there was deterioration in the patients on active treatment with a fall in FEV1. So saying that FEV1 improved more in the placebo limb is incorrect. 4- The mean number of days of treatment in the placebo group is given as 2.3 with CI of 1 to 2 is statistically impossible as mean cannot be greater than 95% CI.

In the discussion section; 1- Firstly saying that the study was adequately powered is incorrect. 2- As the recording of baseline parameters was done late in the management pathway, this would make the patients less breathless with a lower symptom score. So the potential of improvement between active and placebo groups will be small and would favour placebo group (type 1 error), but no mention of this has been made in the discussion. 3- The fact the previous studies like YONIV (2) have shown that pH is a very important predictor of mortality. But in the discussion section, the fact that patients on active treatment had a statistically significant improvement in pH, is described only as 'slightly higher'. This suggests that according to authors any significant result of any intervention could be overlooked if the result goes against their line of reasoning.

The statement that ONE investigator saw each and every patient (320) within 4 hours of admission is physically impossible.

Using professor Town to write the accompanying editorial showed poor judgement on behalf of the editors, as he is clearly biased against use of aminophylline. In the accompanying editorial (3), professor Town gives 2 references of guidelines, which recommend that aminophylline should not be used. I am sure that even professor Town knows that these recommendations are based on grade D evidence, which means that they are not based on evidence but on a group consensus and therefore, do not have true evidence base. Ideally grade D recommendations should be taken out of guideline writing process. The fact that Professor Town did not find any errors in the study (design / results / interpretation), suggests that he has let his personnel bias cloud his judgements.

But all is not lost as there are 2 very important positive conclusions from this study namely:

Firstly it has been shown that use of aminophylline is not associated with any major side effects. Secondly the fact that aminophylline therapy improved the pH in the active treatment group, suggests that aminophylline could be used as initial management of acidotic COPD patients, till NIV is being arranged.

After performing such a poorly designed and biased study, expecting it to be published in the 2nd highest rated thoracic journal is bad but it was shocking to see it published.

There is however, one very amusing fact, in a hospital where the COPD team obviously believes that aminophylline does not work, usage of aminophylline was the second commonest reason for 'non-eligibility for the trial' in patients with exacerbation of COPD.

References

1. Duffy N, Walker P, Diamantea F et al. Intravenous aminophylline in patients admitted to hospital with non-acidotic exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Thorax 2005; 60: 713-7

2. Plank P, Owen J, Elliott M. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000; 355:1931-5

3. Town G. Aminophylline for COPD exacerbations? Not usually. Thorax 2005; 60: 709

Dear Editor,

Ghuysen et al in their recent retrospective study demonstrated the potential value of CTPA RV/LV ratio in predicting in-hospital mortality related to pulmonary embolism.[1] I wondered if they assessed ECG evidence of acute right heart strain and/or serum cardiac biomarkers of injury in the same study and what the relative prognostic value of these indices versus the CTPA RV/LV ratio was, assuming that the ability to correlate with the degree of RV dysfunction is the most important factor here.

Yours sincerely,

Andrew RL Medford

References:

1. Ghuysen A, Ghaye B, Willems V et al. Computed tomographic pulmonary angiography and prognostic significance in patients with acute pulmonary embolism. Thorax 2005; 60: 956-61.