462 EDITORIALS persistent inflammation in bronchial macrophages. There have been few 5 Kinnula VL. Focus on antioxidant enzymes and antioxidant strategies in smoking related biopsy specimens, while the number of attempts at targeting oxidative stress via airway disease. Thorax 2005;60:693–700. Thorax: first published as 10.1136/thx.2005.052670 on 31 May 2006. Downloaded from sputum neutrophils and lymphocytes supplementing antioxidants or boosting 6 Di Stefano A, Caramori G, Ricciardolo FL, et al. and the levels of interleukin-8 and endogenous levels in the older smoker, Cellular and molecular mechanisms in chronic obstructive pulmonary disease: an overview. Clin eosinophilic cationic protein actually but this certainly should be evaluated. Exp Allergy 2004;34:1156–67. increased at 1 year. The duration of As already mentioned, the benefits of 7 Hogg JC, Chu F, Utokaparch S, et al. The nature smoking cessation is also important smoking cessation can be seen regardless of small-airway obstruction in chronic obstructive of age and include a decreased rate of pulmonary disease. N Engl J Med because, with a longer duration, the 2004;350:2645–53. CD8 cell numbers decrease, plasma cell decline in FEV1, a lower risk of stroke or 8 Hodge S, Hodge G, Holmes M, et al. Increased numbers increase, while other inflam- myocardial infarction, and meaningful airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation. Eur Respir J 14 life extension. Surprisingly, the elderly matory cells persist. Since oxidative 2005;25:447–54. stress (as reflected in protein carbonyl are less likely to receive smoking cessa- 9 Morris A, Sciurba FC, Lebedeva IP. levels) also persists after smoking cessa- tion advice than their younger counter- Association of chronic obstructive pulmonary parts.17 Clearly, as more research is disease severity and pneumocystis tion, the relationship between oxidative colonization. Am J Respir Crit Care Med stress, duration of cessation, and inflam- performed on pathogenetic mechanisms 2004;170:408–13. matory markers needs further study. such as oxidative stress in the elderly 10 Retamales I, Elliott WM, Meshi B, et al. smoker, simultaneous attention must be Amplification of inflammation in emphysema There has been renewed interest in and its association with latent adenoviral obstructive lung disease in the elderly. paid to prevention. infection. Am J Respir Crit Care Med This population is at an increased risk of Thorax 2006;61:461–462. 2001;164:469–73. 11 Agusti A, MacNee W, Donaldson K. Hypothesis: both pulmonary and systemic injury doi: 10.1136/thx.2005.053058 Does COPD have an autoimmune component? from tobacco smoke. The Health Aging Thorax 2003;58:832–4. Correspondence to: Dr J F Donohue, Professor and Body Composition study is a pro- 12 Willemse BW, ten Hacken NH, Rutgers B, et al. of Medicine, Division of Pulmonary Diseases Effect of 1-year smoking cessation on airway spective cohort of individuals aged 70– and Critical Care Medicine, University of North inflammation in COPD and asymptomatic 79 years. In well functioning elderly Carolina at Chapel Hill, NC 27599-7020, smokers. Eur Respir J 2005;26:835–45. subjects with or without obstructive USA; [email protected] 13 Rutgers SR, Postma DS, ten Hacken NH, et al. Ongoing airway inflammation in patients with lung disease, interleukin-6 is associated Funding: none. COPD who do not currently smoke. Thorax with reduced FEV1, quadriceps strength, Competing interests: none declared. 2000;55:12–8. and exercise capacity.15 The findings of 14 Lapperre TS, Postma DS, Gosman MM, et al. Relation between duration of smoking cessation Nagai et al add the possibility that and bronchial inflammation in COPD. Thorax increasing oxidative stress with age REFERENCES 2006;61:115–21. may also contribute. 15 Yende S, Waterer GW, Tolley EA, et al. 1 Pauwels RA, Rabe KF. Burden and clinical Inflammatory markers are associated Perhaps the finding that oxidative features of chronic obstructive pulmonary disease with ventilatory limitation and muscle stress increases with age is not too (COPD). Lancet 2004;364:613–20. dysfunction in obstructive lung disease in well 2 Nagai K, Betsuyaku T, Kondo T, et al. Long term surprising. Older smokers are exposed functioning elderly subjects. Thorax smoking with age builds up excessive oxidative 2006;61:10–6. to cigarette smoke over many years. stress in bronchoalveolar lavage fluid. Thorax 16 Thomas RA, Green RH, Brightling CE, et al. The Even in a healthy volunteer popula- 2006;61:496–502. influence of age on induced sputum differential tion, neutrophil counts in induced spu- 3 MacNee W. Pulmonary and systemic oxidant/ cell counts in normal subjects. Chest http://thorax.bmj.com/ antioxidant imbalance in chronic obstructive 2004;126:4049–50. 16 tum increased with age, possibly as a pulmonary disease. Proc Am Thorac Soc 17 Buckland A, Connolly MJ. Age-related result of exposure to pollutants. 2005;2:50–60. differences in smoking cessation advice and Smoking leads to age related decreases 4 Bowler RP, Barnes PJ, Crapo JD. The role of support given to patients hospitalized with oxidative stress in chronic obstructive pulmonary smoking-related illness. Age Ageing in antioxidant activity in alveolar disease. 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Post-infectious bronchiolitis obliterans in children constrictive bronchiolitis are a common on September 26, 2021 by guest. Protected copyright...... end point for many disorders that are associated with airway epithelial injury including allograft recipients (lung, Insights into post-infectious bronchiolitis heart-lung, and bone marrow), previous lower respiratory tract infection (adeno- obliterans in children virus,3–6 influenza,7 parainfluenza, measles, respiratory syncytial virus,8 or K J Smith, L L Fan Mycoplamsa pneumoniae9–11), collagen vas- cular disease (especially rheumatoid ...... arthritis and Sjogren’s syndrome), toxic New information contributing to our understanding of risk factors fume inhalation, chronic hypersensitiv- ity pneumonitis, drugs (such as penicil- predisposing to bronchiolitis obliterans in children lamine or cocaine), and Stevens- Johnson syndrome.12 13 With the excep- ronchiolitis obliterans (BO) is a are recognised, and these may be part of tion of specialised centres where large rare form of chronic obstructive a continuum. Proliferative bronchiolitis numbers of paediatric lung, heart-lung, lung disease that follows an insult is characterised by intraluminal exu- or bone marrow transplants are per- B 1 to the lower respiratory tract. It is dates, whereas constrictive bronchiolitis formed, post-infectious BO is generally characterised by inflammation and is characterised by alterations in the the most common form of BO in fibrosis of the terminal and respiratory walls of the bronchioles ranging from children worldwide. bronchioles that lead to narrowing and/ inflammation to fibrosis and, ulti- For unclear reasons, post-infectious or complete obliteration of the airway mately, to complete obliteration of the BO seems to occur more frequently in lumen. Pathologically, two forms of BO lumen.2 The histological findings of the southern hemisphere (Argentina,

www.thoraxjnl.com EDITORIALS 463

Chile, New Zealand, and Australia), but decreased pulmonary distensibility, and REFERENCES Thorax: first published as 10.1136/thx.2005.052670 on 31 May 2006. Downloaded from it is also found in other parts of the increased airway resistance. They con- 1 Kurland G, Michelson P. Bronchiolitis obliterans world. Genetic factors may play a role in cluded that their findings might repre- in children. Pediatr Pulmonol 2005;39:193–208. that the prevalence of BO appears to be sent the functional expression of the 2 Myers JL, Colby TV. Pathological manifestations of bronchiolitis, constrictive bronchiolitis, increased in Native Americans in histopathological damage of BO. Since cryptogenic organizing pneumonia and diffuse Canada,14 15 Polynesians in New lung biopsies are often non-diagnostic panbronchiolitis. Clin Chest Med Zealand,16 and Native Koreans.11 A in BO and carry risks, the clinical 1993;14:611–22. 3 Teper AM, Kofman CD, Maffey AF, et al. Lung recent study found that HLA- definition developed by the authors, function in infants with chronic pulmonary disease DQB1*0302, an antigen highly repre- although imperfect, seems appropriate after severe adenoviral illness. J Pediatr sented in Amerindians, was increased in to identify the cohort of children who 1999;134:730–3. 17 4 Becroft DM. Bronchiolitis obliterans, children with BO in Argentina. developed severe post-infectious bronchiectasis, and other sequelae of adenovirus In this issue of Thorax Colom et al18 obstructive lung disease in the current type 21 infection in young children. J Clin Pathol present the first systematic study exam- study. 1971;24:72–82. 5 Simila S, Linna O, Lanning P, et al. Chronic lung ining the risk factors associated with the Although not a primary focus of this damage caused by adenovirus type 7: a ten-year development of BO in children. Given study, one additional interesting and follow-up study. Chest 1981;80:127–31. the relatively high incidence of BO in important observation was the excellent 6 Sly PD, Soto-Quiros ME, Landau LI, et al. Factors predisposing to abnormal pulmonary function Argentina, the authors have accumu- long term outcome of the patients with after adenovirus type 7 pneumonia. Arch Dis lated extensive experience with this BO. This finding supports the impres- Child 1984;59:935–9. disorder and have a unique opportunity sion of many of us that post-infectious 7 Laraya-Cuasay LR, DeForest A, Huff D, et al. to study this relatively rare disease. Chronic pulmonary complications of early BO in children carries a better prognosis influenza virus infection in children. Am Rev Although the association between ade- than other forms of BO, particularly Respir Dis 1977;116:617–25. novirus infection and BO in children has those that occur in adults. Given the 8 Krasinski K. Severe respiratory syncytial virus been well recognised,41115 this study infection: clinical features, nosocomial acquisition limitations of its retrospective design, and outcome. Pediatr Infect Dis 1985;4:250–7. convincingly shows that adenovirus is this study represents a good first step in 9 Prabhu MB, Barber D, Cockcroft DW. by far the most common cause of post- the systematic evaluation of children Bronchiolitis obliterans and Mycoplasma infectious BO. The additional finding pneumonia. Respir Med 1991;85:535–7. with BO. Whether these findings can be 10 Coultas DB, Samet JM, Butler C. Bronchiolitis that mechanical ventilation is an inde- extrapolated to BO in other parts of the obliterans due to Mycoplasma pneumoniae. pendent risk factor for the development world remains to be seen. West J Med 1986;144:471–4. of BO is not surprising, but this associa- 11 Kim CK, Kim SW, Kim JS, et al. Bronchiolitis Further research is needed to ascer- obliterans in the 1990s in Korea and the United tion has never been previously exam- tain the mechanisms by which adeno- States. Chest 2001;120:1101–6. ined. The authors are careful to point 12 Kim MJ, Lee KY. Bronchiolitis obliterans in virus—more than other respiratory out that their data do not allow them to children with Stevens-Johnson syndrome: follow- pathogens—contributes to the develop- determine whether mechanical ventila- up with high resolution CT. Pediatr Radiol ment of BO. Additional investigations 1996;26:22–5. tion contributes to the development Hansell DM should be done to define more clearly 13 . Small airways diseases: detection of BO or simply reflects the severity of and insights with computed tomography. Eur the specific value of clinical presenta- Respir J 2001;17:1294–313. the acute insult. This paper therefore 14 Wohl ME, Chernick V. State of the art:

tion, pulmonary function testing, high http://thorax.bmj.com/ presents important new information resolution computed tomography, and bronchiolitis. Am Rev Respir Dis that contributes to our understanding 1978;118:759–81. lung biopsy in the diagnosis of BO in 15 Cumming GR, Macpherson RI, Chernick V. of risk factors predisposing to BO in Unilateral hyperlucent lung syndrome in children. children. children. Surrogate markers of disease activity need to be developed. For J Pediatr 1971;78:250–60. Formally evaluating this rare disease 16 Lang WR, Howden CW, Laws J, et al. example, preliminary studies suggest Bronchopneumonia with serious sequelae in is problematic for many reasons. Most that KL-6, a protein expressed by children with evidence of adenovirus type 21 importantly, perhaps, is that no single infection. BMJ 1969;1:73–9. classification scheme has been widely activated pulmonary epithelial cells, is 17 Teper AM, Marcos CY, Theiler G, et al. accepted. Pathological,2 clinical,19 20 and increased in the serum of lung trans- Association between HLA and the incidence of 24 bronchiolitis obliterans (BO) in Argentina. on September 26, 2021 by guest. Protected copyright. 21 plant patients who develop BO. radiological classification schemes Am J Respir Crit Care Med 2004;169:A382. have been proposed, mainly for BO in Whether KL-6 would be a useful marker 18 Colom AJ, Teper AM, Vollmer WM, et al. Risk adults. Although the histopathological in post-infectious BO should be evalu- factors for the development of post-infectious ated. Finally, systematic studies are bronchiolitis obliterans in children with subtypes can be classified by the pathol- bronchiolitis. Thorax 2006;61:503–6. ogists, the clinical and radiological needed to determine if treatments such 19 Epler GR, Colby TV. The spectrum of bronchiolitis 25 26 correlates are not always obvious. as infliximab and azithromycin, sug- obliterans. Chest 1983;83:161–2. gested for other forms of BO, are 20 Turton CW, Williams G, Green M. Cryptogenic Furthermore, even though histopathol- obliterative bronchiolitis in adults. Thorax ogy is considered the gold standard for effective in improving the outcome of 1981;36:805–10. diagnosis, the non-homogenous distri- patients with post-infectious BO. 21 Muller NL, Miller RR. Diseases of the bronchioles: CT and histopathologic findings. Radiology bution of pathology in the affected lung Thorax 2006;61:462–463. 1995;196:3–12. can lead to sampling error when doi: 10.1136/thx.2005.052670 22 McLoud TC, Epler GR, Colby TV, et al. attempting to diagnose BO by Bronchiolitis obliterans. Radiology 22 23 ...... 1986;159:1–8. biopsy. Thus, definitively diagnosing 23 Panitch HB, Callahan CW Jr, Schidlow DV. this disorder remains problematic, even Authors’ affiliations Bronchiolitis in children. Clin Chest Med with lung biopsy. In this study the K J Smith, L L Fan, Department of Pediatric 1993;14:715–31. Pulmonology, Baylor College of Medicine, 24 Walter JN, Doan M, Zhang H, et al. Serum KL-6 authors chose to define BO using as a marker for bronchiolitis obliterans after lung clinical criteria that they had used Texas Children’s Hospital, Houston, TX, USA transplantation. Chest 2005;128:211S. previously to describe the clinical signs 25 Fullmer JJ, Fan LL, Dishop MK, et al. Successful and symptoms associated with chronic Correspondence to: Dr L L Fan, Pulmonary treatment of bronchiolitis obliterans in a bone Medicine Service, Texas Children’s Hospital, marrow transplant patient with tumor necrosis pulmonary disease following severe factor-alpha blockade. Pediatrics 3 6621 Fannin, CC1040.00, Houston, TX 2005;116:767–70. adenoviral illness in children. Using 77030, USA; [email protected] infant lung function techniques, they 26 Shitrit D, Bendayan D, Gidon S, et al. Long-term Funding: none. azithromycin use for treatment of bronchiolitis found that these young children had obliterans syndrome in lung transplant recipients. severe fixed bronchial obstruction, Competing interests: none declared. J Heart Lung Transplant 2005;24:1440–3.

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