Pleural controversy: Aetiology of pneumothoraxresp_

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1 INVITED REVIEW SERIES: PLEURAL DISEASE SERIES EDITORS: JOSÉ M. PORCEL AND Y.C. GARY LEE Pleural controversy: Aetiology of pneumothoraxresp_ DEMONDES HAYNES AND MICHAEL H. BAUMANN Division of Pulmonary and Critical Care Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA ABSTRACT Pneumothoraces are classified as spontaneous, traumatic and iatrogenic. Spontaneous pneumothoraces that occur without recognized lung disease are termed primary spontaneous pneumothoraces (PSP), whereas those that occur due to an underlying lung disease are termed secondary spontaneous pneumothoraces. The aetiology of secondary, traumatic or iatrogenic pneumothoraces is not usually debated. However, the aetiology of PSP is potentially controversial and often debated. Therefore, PSP is the focus of this article. There are several purported causes, which include blebs, bullae, emphysema-like changes (ELC) and pleural porosity. The controversy is valid because of the importance of recurrence prevention. This article reviews the current available evidence for the causes of PSP. The causes of PSP are likely a combination ELC, pleural porosity and other potential factors. Key words: computed tomography, emphysema-like changes, fluorescein-enhanced autofluorescence thoracoscopy, primary spontaneous pneumothorax, secondary spontaneous pneumothorax, spontaneous pneumothorax, The American College of Chest Physicians. INTRODUCTION A pneumothorax is air within the pleural space. A textbook of pleural disease, pulmonary medicine textbook and journal reviews continue to subdivide pneumothoraces 1 3 into traumatic and spontaneous, despite confusion arising from this classification system. Traumatic pneumothoraces occur as a result of direct or indirect trauma to the chest including that The Authors: Dr Haynes is fellowship program director and medical director of respiratory care services. His interests include pleural disease, pulmonary hypertension and medical education. Dr Baumann is Chief Quality Officer and his interests include pleural disease and quality measures. Correspondence: Demondes Haynes, Division of Pulmonary and Critical Care Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS , USA. dhaynes@umc.edu Received 24 February 2011; accepted 2 March which may occur during procedures. Traumatic pneumothoraces resulting from procedures are termed iatrogenic pneumothoraces. Spontaneous pneumothoraces occur without preceding trauma or an obvious underlying precipitating cause and are sub-classified into primary and secondary. Primary spontaneous pneumothoraces (PSP) arise in patients without clinically apparent lung disease. Secondary spontaneous pneumothoraces (SSP) occur in patients with underlying lung disease, most commonly chronic obstructive lung disease. Confusion arises with this classification system particularly regarding PSP. Therefore, PSP is the focus of this article. Although PSP arise in patients without clinically apparent lung disease, patients with PSP frequently show emphysema-like changes (ELC) on chest CT. Studies show >80% of scanned patients 4 and up to 79% of patients undergoing surgical evaluation have ELC. 2 A pulmonary diseases textbook chapter and a pleural diseases text continue to implicate these ELC (synonymous with blebs and bullae for the remainder of this discussion) as the aetiological cause of PSP. 1,2 Information is becoming better recognized regarding pleural porosity and its role in PSP aetiology. 5 7 Pleural porosity is believed to involve the visceral pleura where mesothelial cells may be replaced by an inflammatory cell layer with increased porosity. This porosity is thought to allow and contribute to air leakage into the pleural space. 8 PSP is the focus of this article given the potential ambiguity regarding PSP aetiology. The role of ELC is debated 9,10 in part because of the potential treatment implications. The goals of treatment of PSP are the drainage of pleural air and the prevention of future recurrences. 11,12 The American College of Chest Physicians (ACCP) spontaneous pneumothorax (SP) management guidelines make recommendations regarding recurrence prevention and incorporate the size of the pneumothorax and the accompanying degree of symptoms (stability) to select from various immediate treatment options. Eighty-five per cent of the thirty-two international pneumothorax experts surveyed recommend recurrence prevention after a second occurrence of a PSP; the remaining 15% felt recurrence prevention should be offered after the first PSP event. 12 Surgical doi: /j x

2 Pneumothorax aetiology 605 intervention to prevent PSP recurrence is recommended with a thoracoscopic approach preferred. The ACCP pneumothorax statement, with very good consensus, notes that forgoing bleb/bullous (i.e. ELC) intervention (resection) in a patient with a PSP is inappropriate. Thoracoscopically directed staple bullectomy accompanied by parietal pleural abrasion is the preferred recurrence prevention method. 12 Such emphasis on the removal of ELC highlights the aetiological importance placed upon lung blebs (and bullae) in the pathogenesis of PSP. More recently, the British Thoracic Society pleural disease guideline 13 also makes recommendations regarding recurrence prevention. They note that surgical options are more effective than chemical pleurodesis alone. The objectives in the surgical approach are to resect or obliterate ELC and pleural porosities and also to create a symphysis between the two pleural surfaces. If patients are too ill or unwilling to undergo surgical recurrence prevention, then medical (chemical) pleurodesis should be considered. 13 Open thoracotomy may have a lower recurrence rate as opposed VATS. This difference was found in a meta-analysis of randomized and nonrandomized trials. A meta-analysis including only the randomized trials did not reveal this difference. 14 Vohra and colleagues concluded that VATS pleurectomy is comparable to open pleurectomy in treatment of SP, and they assert that VATS appears to have lower morbidity and less duration of hospitalization. 14 There is support for the central role of ELC in the genesis of PSP. The evidence to date is circumstantial as direct evidence for the aetiological rupture of a lung bleb or bullous lesion as the cause of a PSP has not been shown. Blebs and bullae may not be the only aetiological factors involved in the development of a PSP as suggested in a thoracoscopic study by Noppen where he discusses pleural porosity and its contribution to PSP occurrence. 6 Blebs and bullae are, however, the most immediately obvious cause of a PSP and cannot and should not be easily dismissed. CT CHEST EVALUATION OF ELC The strongest evidence of the aetiological association of PSP and ELC appears to be found in the information provided by CT of the chest. Bense and colleagues study of non-alpha-1-antitrypsin deficient, non-smoking patients found ELC in 81% of patients suffering a PSP while no such changes were noted in control patients. 15 Such CT-delineated ELC are often bilateral and predominantly, but not solely, located in the upper lung zone These findings may also predict the likelihood of PSP occurrence, a finding in Bense and colleagues study. 15 Warner and colleagues prospective evaluation using a CT-derived ELC score found the ELC score in the ipsilateral lung significantly greater in the PSP patients with a recurrence. 18 However, due to the limited number of patients, an absolute number of blebs, size of blebs or the ELC score could not define an absolute risk of PSP recurrence. Notably, these key CT data are overlooked by F. Schramel, a challenger of the aetiological role of ELC in PSP, in a review 19 and rebuttal 20 to two publications supporting the aetiological role of ELC in PSP. 21,22 Other studies add support to the aetiological role of ELC in PSP. Lesur and colleagues note that emphysematous lesions were significantly more common in PSP patients than in age, gender and smoking matched controls. 16 Senac and colleagues observed the number and size of bullae as well as whether they were bulging or without surrounding fibrosis were markers of high recurrence risk. 23 Based upon such CT evidence regarding the potential aetiological role of ELC, some surgeons utilize high-resolution CT (HRCT) evidence of blebs larger than 5 mm to select patients with an initial PSP for early operative intervention. 24 Sihoe and colleagues provide compelling CT data supporting the role of ELC in the development of PSP. 21,22 The authors find a statistically significant (P = 0.017) association of CT detected presence of lung bullae in the contralateral lung following a unilateral PSP and a higher rate of subsequent pneumothorax occurrence in the contralateral hemithorax. Of the 28 PSP patients studied, 15 had contralateral bullae and 6 of these (40%) had a subsequent pneumothorax in the contralateral hemithorax; none of the 13 patients with PSP without contralateral bullae developed pneumothorax on the contralateral side during a mean follow up of more than 59 months. Questions were posed about the statistical significance of this study; however, these questions have been answered satisfactorily with the additional follow up of patients and recalculation of the statistics after the study concluded. 25,26 This study supports the role of CT scanning in PSP as a possible recurrence prediction tool. 27 More recently, Huang and colleagues provide more compelling data that support ELC as causative factors in PSP. HRCT chest was performed in the 231 patients (282 PSP) with a mean of 92 months for the duration of follow up. This is a retrospective study performed at one location. The HRCT scanning protocol included 1 mm thickness cuts every 5 mm. The patients served as their own contralateral self controls. Thirty-three patients (14.29%) had contralateral recurrence of PSP. All patients with contralateral pneumothorax had ELC present on HRCT (P < 0.001), and there was no association with gender or smoking. However, multiple logistic regression analysis revealed that being underweight (BMI < 18.5 kg/m 2 ) is an independent risk factor for contralateral recurrence. 28 This study supports the use of HRCT scans in assessing risk of recurrence and the option of single-stage bilateral VATS for recurrence prevention, especially for those individuals who are at high risk for recurrent PSP (aviators, divers, etc.) This study adds credence to the belief that underweight PSP patients with HRCT evidence of ELC in the ipsilateral or contralateral lung should be strongly considered for recurrence prevention. 27 Conversely, several other CT studies cast limited doubt on the role of ELC in PSP development. A study by Mitlehner and colleagues of 35 patients using conventional CT chest found no correlation between ELC

3 606 in first-time PSP patients versus those patients with a recurrent PSP. 17 Negative aspects of this study include a lack of controls and poor delineation of the patients with a recurrence. Additionally, the CT method utilized is suboptimal given the lack of high-resolution scanning. High-resolution scanning, defined in part by narrow collimation, is significantly more accurate for detecting ELC. 4 Additionally, Smit, Schramel and colleagues reported a similar study incorporating highresolution scanning. There were 101 cases of PSP; however, there was no control group or patient follow up. 29 The presence of ELC in those with a first versus a recurrent PSP was compared incorporating the premise that if ELC predispose to the development of PSP, a higher incidence of ELC should be noted in patients with recurrent PSP. There was no difference in the presence of ELC between the first-time PSP group and the recurrent PSP group. The authors note that this study cannot answer the question as to whether ELC are the cause of PSP given the absence of a control group. This study also does not disprove that ECL predispose to PSP recurrence. A flawed assumption is shared by both the Mitlehner and Smit studies: if ELC are the aetiology of PSP, they should be more prevalent in patients suffering a recurrent PSP as opposed to first-time PSP patients. Instead, the prevalence of ELC in patients suffering a first occurrence of PSP compared with patients having a recurrence may not be, and perhaps should not be, different if ELC are the aetiology of PSP. Notably, no difference in ELC prevalence is the key finding of both the Mitlehner and Smit studies. Yim and colleagues similarly highlight the same flaw in their letter to the editor 26 responding to Schramel and colleagues criticism of their controlled CT study affirming an aetiological role for ELC in PSP (discussed above 21,22 ). More recently, a study by Ouanes-Besbes revealed no correlation of a CT-derived dystrophic score of ELC and recurrence of PSP. This study used a scoring system for ELC as opposed to a simple absence or presence of ELC. The scoring system, number of patients, relatively short duration of follow up, and HRCT technique could all influence the results of this study. 30 SURGICAL EVALUATION OF ELC The surgical literature, including thoracoscopic approaches, provides additional evidence regarding the role that ELC play in the development of PSP. This area is subject to great variation in interpretation. Thoracoscopic staging of ELC, which are thought to be causative of SP, is often noted as integral to management of patients with SP. 31 The commonly used macroscopic stages visualized by thoracoscopy are: stage I normal visceral pleura; stage II some pleural adhesions; stage III blebs or bullae (emphysema like changes) <2 cm in diameter; and stage IV bullae >2 cm in diameter Approximately half of SP patients will be stages I and II and the other half stages III and IV. 31 D Haynes and MH Baumann However, controversy and disagreement remain regarding the aetiological role of such ELC changes seen during thoracoscopy in the development of PSP. One author, F. Schramel, outlines his arguments against the aetiological role of ELC in PSP in a review 19 and in a letter to the editor. 20 Central to Schramel s argument is the thoracoscopic study by Janssen, Schramel and colleagues of SP patients. 35 This surgical study adopts the same flawed premise as that of the CT study discussed above: if ELC are the aetiology of PSP, ELC should be more prevalent in patients suffering a recurrent PSP than in patients with a firsttime PSP. Janssen and colleagues found no significant difference in the thoracoscopic appearance of the first-time and recurrent PSP. 35 Schramel incorporates these findings to dispute the role of ELC in PSP development. An SP review by Sahn and Heffner notes that higher pneumothorax recurrence rates with VATS (2 14%) compared with limited thoracotomy (often less than 1%) 36 may be due to inadequate exposure of the chest cavity impeding detection and resection of ELC. Horio and colleagues conducted a retrospective study supporting this assertion. They found a significantly larger number of resected ELC in the thoracotomy group compared with the thoracoscopy group (P = 0.02). 37 Several non-randomized studies evaluate patients undergoing ELC removal and pleurodesis and patients undergoing pleurodesis alone. 33,34,38,39 Studies by Tschopp and colleagues 33 and Noppen and colleagues 34 assess the potential role of thoracoscopic talc poudrage alone for recurrence prevention in SP patients including PSP patients. Tschopp and colleagues study of serial patients found medical thoracoscopy directed talc pleurodesis without any directed therapy for ELC provided 95% recurrence prevention for a mean follow up of 5 years in 89 SP patients, 61 with PSP. ELC, however, still play a role in recurrence. Only the last 59 of the 89 patients underwent macroscopic staging. Of these, there were 20 stage I, 11 stage II, 18 stage III and 10 stage IV. In the stage IV patients, four relapsed (40% recurrence rate) and two required surgical intervention (repeat pleurodesis or thoracotomy). The risk of definitive failure requiring surgery in this group was significantly higher than in those without bullae (odds ratio 7, P = 0.03). Of note, the distribution of PSP versus SSP in this group was not defined. Regardless, the presence of blebs >2 cm was associated with a poorer outcome and a high pneumothorax recurrence rate. Noppen and colleagues presented similar findings from their non-randomized study noting 6.5% and 8.7% recurrence rates in PSP (n = 29) and SSP (n = 20) patients, respectively, undergoing thoracoscopic talc poudrage. 34 Notably, all ELC >2 cm (stage IV) were treated with thermocoagulation in addition to talc poudrage. Eleven of 29 PSP patients (38%) were stage IV patients. In aggregate, these studies indicate that incorporating talc poudrage alone without addressing smaller (<2 cm) ELC provides good pneumothorax recurrence prevention. However, the data do not indicate that the smaller ELC would not have lead to pneumothorax recurrence if talc poudrage had not

4 Pneumothorax aetiology 607 been performed. Not removing larger bullae (>2 cm) even in the face of talc poudrage may lead up to a 40% recurrence rate. A third study by Loubani and Lynch 39 reveals similar findings when examined closely. Patients were enrolled serially and the initial 25 of 49 patients underwent thoracoscopic bullectomy alone and the remaining 24 patients underwent bullectomy and pleurodesis with tetracycline. Recurrence rates were higher in the bullectomy alone group (20%) compared with the bullectomy combined with tetracycline pleurodesis group (4%). The authors noted during the serial patient enrolment that the bullectomy alone group was having high recurrence rate of 20%. They state that this recurrence rate combined with the fact that in some cases a large number of tiny blebs were present, especially on the sharp margins of the lung, and were technically difficult to remove, led us to introduce chemical pleurodesis. 39 Thus, unresected ELC are likely the cause of failed recurrence prevention by bullectomy alone. The authors consequently added pleurodesis to bullectomy to prevent rupture of residual ELC. These publications suggest a reasonable therapeutic option for SP patients to medical thoracoscopists who incorporate conscious sedation in the nonoperating room environment (versus the traditional operating room-based video-assisted thoracoscopic surgical approach using general anaesthesia and multiple entry ports). The medical thoracoscopist can offer significant recurrence prevention by talc poudrage in patients with ELC <2 cm in size without surgically manipulating the lung. The use of thermocoagulation provides a readily accessible addition to talc poudrage for the medical thoracoscopist in patients with blebs >2 cm. 40 Additional indirect surgical evidence that supports ELC as possible cause in PSP is provided in a study by Amjadi and colleagues. 41 Two-hundred and fifty patients were enrolled in this prospective study and followed for up to 9 years. These individuals underwent thoracoscopic thoracic sympathectomy (TTS) as treatment for essential hyperhydrosis. None of the enrolled patients had any previous pulmonary history including a history of PSP. At the time of the TTS, a complete thoracoscopic evaluation was performed bilaterally, and the presence of blebs or bullae, their number and locations were documented. No therapeutic action regarding the blebs was taken. Blebs were identified in 6% of the patients. There was no association with gender, and 46% of the patients were smokers. Lower BMI was a risk factor for development of blebs. This is consistent with previous reports that low BMI and smoking are risk factors for development of PSP However, the prevalence of blebs is lower in this study and is likely related to the decreased smoking prevalence of 46% (and most less than 5-pack year history) compared with 85% found by Lesur and colleagues. 16 Additionally, the association between a lower BMI and more blebs is consistent with the lower BMI and blebs noted in the Huang study. 28 Interestingly, Amjadi and colleagues argue against blebs being precursors to PSP. 41 The preceding surgical studies do not refute ELC as causative in the development of PSP. Conversely, they provide further evidence that ELC play a key role in the development and recurrence of PSP. PLEURAL POROSITY CAUSAL EVIDENCE Additional information regarding aetiology of PSP is provided by Noppen and colleagues. 6,7 They further delineate the concept of pleural porosity. Initially, they describe a case report in which a patient inhaled aerosolized fluorescein min before thoracoscopy. 7 They discovered that areas which appeared normal at white light thoracoscopy (WLT) were abnormal with fluorescein-enhanced autofluorescence thoracoscopy (FEAT). Subsequently, they compared 12 PSP patients with 17 non-psp (patients with essential hydrosis). 6 All patients underwent WLT and FEAT. FEAT reveals significantly more parenchymal abnormalities than seen with WLT. High-grade FEAT lesions were exclusively present in PSP and predominantly at lung zones that appeared normal at WLT. The authors did not correct for multiple comparisons. When using the Bonferroni correction for multiple comparisons, the only remaining statistically significant findings were more high-grade FEAT lesions and blebs/bullae in the PSP group compared with the control group. Notably, the FEAT scoring was semiquantitative and unblinded though scoring was verified by another provider. This study adds evidence as to why pleurodesis combined with surgical bullectomy is superior to surgical bullectomy alone for recurrence prevention. There are lesions and areas of potential air leakage seen by FEAT that may not be seen with WLT alone, and areas that are distinct from the ELC. These areas may best be addressed by pleurodesis. Further study in this area is warranted. MISCELLANEOUS CAUSAL EVIDENCE Additional indirect evidence supporting the aetiological role of ELC in PSP development includes the association with smoking, morphometric evidence, genetic evidence, atmospheric evidence and an association with music. Smoking has been strongly implicated in the pathogenesis of PSP and is associated with a ninefold or greater risk of developing a first PSP. 42 Cottin and colleagues note that respiratory bronchiolitis may be the pathologic process driving the development of PSP (including ELC), with 87% of smokers undergoing a surgical recurrence prevention for PSP showing changes of bronchiolitis. 45 The surgical specimens examined in these PSP patients were resected blebs, bullae or air leaks with the underlying adjacent lung parenchyma. 45 The geographic proximity of these ELC and respiratory bronchiolitis implicates bronchiolitis and associated smoking in the pathogenesis of ELC. However, no control patients were enrolled. Unfortunately, despite smoking s strong association with PSP and its likely role in the

5 608 pathogenesis of ELC, more than 80% of PSP patients continue smoking after their first PSP although possessing clear knowledge of the strong link between PSP and smoking. 46 Complementing the findings by Cottin and colleagues are those by Jordan and colleagues noting that most (95%) of SP patients (mixed PSP and SSP patient group) with surgically treated pneumothorax have emphysema or an isolated bulla or bleb (ELC) in the examined surgical specimens. 47 Additionally, Ohata and Suzuki s series of 126 SP patients (apparently mixed PSP and SSP) notes the prevalence of ELC. 5 Two hundred and fifty-three of 334 patients of SP underwent thoracotomy with ELC found in most (no specified percentage) of the patients. One hundred and twenty-six of these 253 ELC underwent light and electron microscopy. Fifty per cent of these specimens revealed evidence of bronchiolitis. Interestingly, mesothelial cells and numerous pore-like structures variably covered the ELC, raising the possibility that frank rupture of an ELC may not be necessary for an SP to occur. This may add support to the concept of pleural porosity in its aetiological role in PSP occurrence. Morphometric assessment of PSP patients may also lend support to the role of ELC in PSP. Once ELC are present, the patient s body type may continue to drive (or even generate) ELC development. This is supported by Coxson and colleagues evidence of early emphysema in patients with anorexia nervosa compared with control patients. 48 Withers and colleagues note that PSP patients (male American military personnel) were 2 inches taller and 25 pounds lighter than the average American men. 43 This ectomorphic body habitus is present from childhood and is primarily driven by the patient s greater-than-average height that is particularly exaggerated in the patient s teens. 49 The rapid increase in vertical dimension of the thorax may increase intrathoracic pressure at the lung apex and drive subpleural cyst (ELC) formation. 49 Light similarly postulates that the gradient of pleural pressure is greater from the lung base to apex in taller individuals subjecting the alveoli at the lung apex to a greater-than-average distending pressure. Over a period of time this pressure gradient could lead to the development of subpleural ELC in taller individuals genetically predisposed to ELC formation. 1 The wellestablished morphometric evidence is further supported in the studies by Huang et al. 28 and Amjadi et al. 41 Although rare, familial patterns of inheritance, including autosomal dominant, continue to be reported for PSP patients and may herald an unrecognized connective tissue disorder 50 perhaps predisposing patients to ELC formation. A report by Morrison and colleagues 50 supports earlier work by Abolnik and colleagues, 51 which identified 15 families through the Israeli Defense Forces in addition to 14 families from the literature with familial primary SP due to primarily to an autosomal dominant gene with incomplete penetrance or a X-linked recessive gene. 51 Additional studies add support to possible candidate gene abnormalities and possible familial links that predispose to PSP. 52,53 Other evidence regarding the role of ELC in PSP development is found in the potential and controversial association of PSP development with atmospheric pressure changes. If atmospheric changes can precipitate PSP, the ELC are the most apparent target of such pressure fluctuations. Several studies support the association of PSP events and atmospheric pressure changes Bense correlated a 10-millibar drop in atmospheric pressure in a 24-h time span with a statistically significant increase in the number of hospital admissions for SP 48 h later. 54 Scott and colleagues found a clear relationship between PSP events and ambient pressure changes supporting the theory that SP develop as result of the rupture of ELC. They postulate that as external pressure falls, the noncommunicating gas within ELC will expand creating a pressure gradient across the wall of the bleb or bullous lesion leading to its rupture. Repeated pressure fluctuations may be more important than absolute pressure changes. 55 Smit and colleagues cast doubt on the association of atmospheric pressures changes but note an association of PSP events with recent thunderstorms and perhaps temperature fluctuations. 57 More recently, Alifano and colleagues provide information from a 4-year study period. 56 They review 294 episodes of PSP of which 84% occurred in 76 clusters. Clusters were defined as the admission of at least two patients with pneumothorax within 3 days of each other. Clusters were associated with wider differences in atmospheric pressure between the index day (first day of the cluster) and the previous day (P = 0.01). There was also an association with PSP and storms (P < ). There was no association with temperature. Although controversial, such information further implicates ELC as the likely target for any atmospheric perturbations that may elicit PSP events. Another interesting potential cause of PSP is music. 58 Noppen and colleagues report a series of five SP in four patients after exposure to loud music. Three of the four patients were smokers. All of the patients had recent exposures to loud music (concerts, large speakers, etc.). Two of the patients were found to have ELC on CT or at thoracoscopy. The other two patients did not have a CT chest or thoracoscopy performed and were treated with simple aspiration. The authors postulate that repetitive pressure changes in the high energy low frequency range of sound exposures lead to rupture of the interface between the alveolar space and the pleural cavity. 58 This adds further potential support to the ELC as the cause of PSP as these are likely sites of rupture after such pressure fluctuations. SUMMARY D Haynes and MH Baumann Although no direct evidence exists that ELC and pleural porosity are the primary culprits in the genesis of PSP events, the circumstantial evidence is considerable. CT evidence, particularly the findings of the studies by Sihoe and colleagues 21 and Huang and colleagues, 28 noting the statistically significant association of contralateral ELC with contralateral occurrences, is the most compelling. Surgical information,

6 Pneumothorax aetiology 609 particularly recurrence rates up to a 40% in PSP patients with ELC >2 cm unresected surgically, adds support to the aetiological role of ELC. The association of PSP with respiratory bronchiolitis and smoking provides a plausible pathogenetic mechanism for the development of ELC. This association with bronchiolitis or other inflammatory process places a greater focus on the potential role of pleural porosity. It is postulated that the visceral pleural mesothelial cells are replaced by an inflammatory cell layer with increased porosity. Further study into this inflammatory process may yield valuable findings. The ELC may independently arise due to the ectomorphic body habitus of many patients with PSP and may be promoted by the pressure gradient created by the abnormally high intrathoracic pressure gradient created by the patient s elongated hemithorax. Such ELC changes may be more likely in genetically predisposed individuals, who are potentially prone to connective tissue abnormalities making the development of ELC more likely. This evidence should not be dismissed unless more compelling evidence clearly negates or substantially minimizes the role of ELC in the development of PSP. Currently, continued surgical resection of ELC is justified and warranted by the available evidence. However, a compromise approach to the PSP patient is performance of talc poudrage alone for patients with ELC all <2 cm or the combination of talc poudrage and surgically directed removal (thermocoagulation or other means) of ELC >2 cm. This application of pleurodesis addresses the growing evidence of pleural porosity as an independent aetiology of PSP. Controversy and debate regarding the aetiology of pneumothorax will likely continue given the numerous studies that both support and argue against ELC as causative in PSP. Moreover, given the present information, there appears to be a role for HRCT (not conventional) in select patients with PSP when considering recurrence prevention. Further investigation will continue regarding the aetiology of PSP. Focus will almost certainly be on smoking, ectomorphic body features, atmospheric pressure changes, ELC and pleural porosity. REFERENCES 1 Light RW. Pneumothorax. In: Light RW (ed.) Pleural Diseases, 5th edn. Lippincott Williams and Wilkins, Philadelphia, PA, 2007; Light RW, Lee GYC. Pneumothorax, chylothorax, hemothorax, and fibrothorax. In: Mason RJ, Broaddus CV, Martin T et al. (eds) Textbook of Respiratory Medicine, 5th edn. W.B. Saunders Company, Philadelphia, PA, 2010; Haynes D, Baumann MH. Management of Pneumothorax. Semin. Respir. Crit. Care Med. 2010; 2010: Muller NL. CT diagnosis of emphysema. It may be accurate, but is it relevant? Chest 1993; 103: Ohata M, Suzuki H. Pathogenesis of spontaneous pneumothorax. With special reference to the ultrastructure of emphysematous bullae. Chest 1980; 77: Noppen M, Dekeukeleire T, Hanon S et al. Fluoresceinenhanced autofluorescence thoracosopy in patients with primary spontaneous pneumothorax and normal subjects. Am. J. Respir. Crit. Care Med. 2006; 174: Noppen M, Stratakos G, Verbanck S et al. Fluorescein-enhanced autofluorescence thoracoscopy in primary spontaneous pneumothorax. Am. J. Respir. Crit. Care Med. 2004; 170: Noppen M, Dekeukeleire T. Pneumothorax. Respiration 2008; 76: Baumann MH. Pro: blebs do cause primary spontaneous pneumothorax. J. Bronchol. 2002; 9: Noppen M. Con: blebs do not cause primary spontaneous pneumothorax. J. Bronchol. 2002; 9: Baumann MH, Strange C. Treatment of spontaneous pneumothorax. A more aggressive approach? Chest 1997; 112: Baumann MH, Strange C, Heffner JE et al. Management of spontaneous pneumothorax. An American College of Chest Physicians Delphi consensus statement. Chest 2001; 119: Macduff A, Arnold A, Harvey J et al. Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline Thorax 2010; 65(Suppl. 2): ii Vohra HA, Adamson L, Weeden DF. Does video-assisted thoracoscopic pleurectomy result in better outcomes than open pleurectomy for primary spontaneous pneumothorax? Interact. Cardiovasc. Thorac. Surg. 2008; 7: Bense L, Lewander R, Eklund G et al. Nonsmoking, non-alpha 1-antitrypsin deficiency-induced emphysema in nonsmokers with healed spontaneous pneumothorax, identified by computed tomography of the lungs. Chest 1993; 103: Lesur O, Delorme N, Fromaget J et al. Computed tomography in the etiologic assessment of idiopathic spontaneous pneumothorax. Chest 1990; 98: Mitlehner W, Friedrich M, Dissmann W. Value of computed tomography in the detection of bullae and blebs in patients with primary spontaneous pneumothorax. Respiration 1992; 59: Warner B, Bailey W, Shipley T. Value of computed tomography of the lung in the management of primary spontaneous pneumothorax. Am. J. Surg. 1991; 162: Schramel F, Postmus P, Vanderschueren R. Current aspects of spontaneous pneumothorax. Eur. Respir. J. 1997; 10: Schramel F, Zanen P. Blebs and/or bullae are of no importance and have no predictive value for recurrences in patients with primary spontaneous pneumothorax. Chest 2001; 119: Sihoe ADL, Yim APC, Lee TW et al. Can CT scanning be used to select patients with unilateral primary spontaneous pneumothorax for bilateral surgery? Chest 2000; 118: Yim APC, Lee TW, Ng CSH et al. CT scanning and bilateral surgery for unilateral primary pneumothorax? Chest 2001; 119: Senac J, Giron J, Aguado J et al. Value of computed tomography for pretherapeutic evaluation of adults with spontaneous idiopathic pneumothorax. Report of twenty-five cases. Ann. Radiol. 1985; 28: Kim J, Kim K, Shim YM et al. Video-assisted thoracic surgery as a primary therapy for primary spontaneous pneumothorax. Decision making by the guideline of high-resolution computed tomography. Surg. Endosc. 1998; 12: Noppen M. CT scanning and bilateral surgery for unilateral primary pneumothorax. Chest 2001; 119: Yim APC, Lee TW, Ng CSH et al. Blebs and/or bullae are of no importance and have no predictive value for recurrences in patients with primary spontaneous pneumothorax. Chest 2001; 119: Baumann MH. To bleb or not to bleb? Chest 2007; 132: Huang T-W, Lee S-C, Cheng Y-L et al. Contralateral recurrence of primary spontaneous pneumothorax. Chest 2007; 132: Smit HJM, Wienk MATP, Schreurs AJM et al. Do bullae indicate a predisposition to recurrent pneumothorax? Br. J. Radiol. 2000; 73:

7 Ouanes-Besbes L, Golli M, Knani J et al. Prediction of recurrent spontaneous pneumothorax: CT scan findings versus management features. Respir. Med. 2007; 101: Boutin C, Astoul P, Rey F et al. Thoracoscopy in the diagnosis and treatment of spontaneous pneumothorax. Clin. Chest Med. 1995; 16: Vanderschueren RGJRA. The role of thoracoscopy in the evaluation and management of pneumothorax. Lung 1990; 168 (Suppl.): Tschopp JM, Brutsche M, Frey JG. Treatment of complicated spontaneous pneumothorax by simple talc pleurodesis under thoracoscopy and local anaesthesia. Thorax 1997; 52: Noppen M, Meysman M, D Haese J et al. Comparison of videoassisted thoracoscopic talcage for recurrent primary versus persistent secondary spontaneous pneumothorax. Eur. Respir. J. 1997; 10: Janssen J, Schramel F, Sutedja T et al. Videothoracoscopic appearance of first and recurrent pneumothorax. Chest 1995; 108: Sahn SA, Heffner JE. Spontaneous pneumothorax. N. Engl. J. Med. 2000; 342: Horio H, Nomori H, Fuyuno G et al. Limited axillary thoracotomy vs video-assisted thoracoscopic surgery for spontaneous pneumothorax. Surg. Endosc. 1998; 12: Hatz RA, Kaps MF, Meimarakis G et al. Long-term results after video-assisted thoracsoscopic surgery for first-time and recurrent spontaneous pneumothorax. Ann. Thorac. Surg. 2000; 70: Loubani B, Lynch V. Video assisted thoracoscopic bullectomy and acromycin pleurodesis: an effective treatment for spontaneous pneumothorax. Respir. Med. 2000; 94: Baumann MH. Medical thoracoscopy-therapy for benign conditions. In: Beamis J, Mathur P, Mehta A (eds) Interventional Pulmonary Medicine. Marcel Dekker, NewYork, 2004; Amjadi K, Alvarez GG, Vanderhelst E et al. The prevalence of blebs or bullae among youg healthy adults: a thoracoscopic investigation. Chest 2007; 132: Bense L, Eklund G, Wiman L-G. Smoking and increased risk of contracting spontaneous pneumothorax. Chest 1987; 92: D Haynes and MH Baumann 43 Withers J, Fishback M, Kiehl P et al. Spontaneous pneumothorax. Am. J. Surg. 1964; 108: Baumann MH, Noppen M. Pneumothorax. Respirology 2004; 9: Cottin V, Streichenberger N, Gamondes J-P et al. Respiratory bronchiolitis in smokers with spontaneous pneumothorax. Eur. Respir. J. 1998; 12: Smit H, Chatrou M, Postmus P. The impact of spontaneous pneumothorax, and its treatment, on the smoking behaviour of young adult smokers. Respir. Med. 1998; 92: Jordan K, Kwong J, Flint J et al. Surgically treated pneumothorax. Radiologic and pathologic findings. Chest 1997; 111: Coxson HO, Chan IH, Mayo JR et al. Early emphysema in patients with anorexia nervosa. Am. J. Respir. Crit. Care Med. 2004; 170: Fujino S, Inoue S, Tezuka N et al. Physical development of surgically treated patients with primary spontaneous pneumothorax. Chest 1999; 116: Morrison P, Lowry R, Nevin N. Familial primary spontaneous pneumothorax consistent with true autosomal dominant inheritance. Thorax 1998; 53: Abolnik IZ, Lossos I, Zlotogora J et al. On the inheritance of primary spontaneous pneumothorax. Am. J. Med. Genet. 1991; 40: Chiu HT, Garcia CK. Familial spontaneous pneumothorax. Curr. Opin. Pulm. Med. 2006; 12: Cardy CM, Maskell NA, Handford PA et al. Familial spontaneous pneumothorax and FBN1 mutations. Am. J. Respir. Crit. Care Med. 2004; 169: Bense L. Spontaneous pneumothorax related to falls in atmospheric pressure. Eur. J. Respir. Dis. 1984; 65: Scott GC, Berger R, Mckean H. The role of atmospheric pressure variation on the development of spontaneous pneumothoraces. Am. Rev. Respir. Dis. 1989; 139: Alifano M, Forti Parri SN, Bonfanti B et al. Atmospheric pressure influences the risk of pneumothorax. Chest 2007; 131: Smit HJM, Deville WL, Schramel FMNH et al. Atmospheric pressure changes and outdoor temperature changes in relation to spontaneous pneumothorax. Chest 1999; 116: Noppen M, Verbanck S, Harvey J et al. Music: a new cause of primary spontaneous pneumothorax. Thorax 2004; 59: