Differential Distribution of Inflammatory Cells in Large and Small Airways in Smokers; S. Battaglia, T. Mauad, A. M. van Schadewijk, A. M. Vignola, K. F. Rabe, V. Bellia, P. J. Sterk, P. S. Hiemstra (J Clin Pathol. 2006; Aug 17; [Epub ahead of print]).
Rationale: Smoking induces structural changes in the airways and is considered as a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease (COPD). However, differences in inflammatory cell distribution between large and small airways have not been systematically explored in smokers. We hypothesized that the content of cells infiltrating the airway wall differs between large and small airways. Aims: We compared the content of neutrophils, macrophages, lymphocytes, and mast cells infiltrating large and small airways in smokers who underwent surgery for lung cancer. Methods: Lung tissue from 15 smokers was analyzed. Inflammatory cells in the lamina propria were identified by immunohistochemistry and quantified by digital image analysis and expressed in number of cells per surface area. Results: The number of neutrophils infiltrating the lamina propria of small airways (median: 225.3 cells/mm(2)) was higher than that in the lamina propria of large airways (median: 60.2 cells/mm(2); p = 0.0001). Similar results were observed for mast cells: 313.3 cells/mm(2) and 133.7 cells/mm(2) in the small and large airways, respectively (p = 0.0002). In contrast, the number of CD4(+) cells was higher in large airways compared to small airways (median: 217.8 versus 80.5 cells/mm(2); p = 0.042). Conclusions: These findings indicate a non-uniform distribution of neutrophils and mast cells throughout the bronchial tree and suggest that these cells may be involved in the development of smoking-related peripheral lung injury. PMID: 16917001 [PubMed—as supplied by publisher].
Comments: There have been reports in the asthma literature that there is a different distribution of inflammatory cells and markers in the small versus large airways, and it has been proposed that this has importance both from a pathogenesis point of view and from a therapeutic point of view. The same can be said for COPD. The small airways are an important target for cigarette smoke and are likely the most vulnerable area for early damage. Characterizing the inflammatory response may guide novel anti-inflammatory interventions that are either delivered systemically or via aerosols that can reach the peripheral airways better than current agents.
Long-Term Follow-up of Patients Receiving Lung-Volume-Reduction Surgery versus Medical Therapy for Severe Emphysema by the National Emphysema Treatment Trial Research Group; K. S. Naunheim, D. E. Wood, Z. Mohsenifar, A. L. Sternberg, G. J. Criner, M. M. DeCamp, C. C. Deschamps, F. J. Martinez, F. C. Sciurba, J. Tonascia, A. P. Fishman; National Emphysema Treatment Trial Research Group (Ann Thorac Surg. 2006 Aug; 82(2):385–387).
Background: The National Emphysema Treatment Trial defined subgroups of patients with severe emphysema in whom lung-volume-reduction surgery (LVRS) improved survival and function at 2 years. Two additional years of follow-up provide valuable information regarding durability. Methods: A total of 1,218 patients with severe emphysema were randomized to receive LVRS or medical treatment. We present updated analyses (4.3 versus 2.4 years median follow-up), including 40% more patients with functional measures 2 years after randomization. Results: The intention-to-treat analysis of 1218 randomized patients demonstrates an overall survival advantage for LVRS, with a 5-year risk ratio (RR) for death of 0.86 (p = 0.02). Improvement was more likely in the LVRS than in the medical group for maximal exercise through 3 years and for health-related quality of life (St. George's Respiratory Questionnaire [SGRQ]) through 4 years. Updated comparisons of survival and functional improvement were consistent with initial results for four clinical subgroups of non-high-risk patients defined by upper-lobe predominance and exercise capacity. After LVRS, the upper-lobe patients with low exercise capacity demonstrated improved survival (5-year RR, 0.67; p = 0.003), exercise throughout 3 years (p < 0.001), and symptoms (SGRQ) through 5 years (p < 0.001 years 1 to 3, p = 0.01 year 5). Upper-lobe-predominant and high-exercise-capacity LVRS patients obtained no survival advantage but were likely to improve exercise capacity (p < 0.01 years 1 to 3) and SGRQ (p < 0.01 years 1 to 4). Conclusions: Effects of LVRS are durable, and it can be recommended for upper-lobe-predominant emphysema patients with low exercise capacity and should be considered for palliation in patients with upper-lobe emphysema and high exercise capacity. PMID: 16888872 [PubMed—indexed for MEDLINE].
Comments: The initial take-home message of the NETT trial—that those with primarily upper lobe disease and low exercise tolerance are the ones most likely to benefit—is extended to four years of monitoring. This further follow-up has also shown that even patients with high exercise capacity find benefit in terms of exercise capacity and respiratory symptoms.
FEV1 /FVC Ratio of 70% Misclassifies Patients with Obstruction at the Extremes of Age. S. D. Roberts, M. O. Farber, K. S. Knox, G. S. Phillips, N. Y. Bhatt, J. G. Mastronarde, K. L. Wood (Chest 2006; 130:200–206).
Background: The American Thoracic Society recommends using the lower limit of normal (LLN) method to diagnose obstructive lung disease. However, few studies have investigated the clinical relevance of these recommendations. We compared the LLN derived from available data sets to a fixed ratio (FEV1/FVC, < 75% or 70%) and also to the FEV1/FVC percent predicted ratio to determine the impact of changing the FEV1/FVC “cutoff” on the spirometric diagnosis of obstructive lung disease. Methods: FEV1, FVC, FEV1/FVC ratio, age, race, sex, height, and weight were recorded from 1,503 pulmonary function tests. Predicted values were calculated using the Third National Health and Nutrition Examination Study data set (Hankinson) and reference values from studies by Crapo, Knudson, and Morris. In addition, the LLN of the FEV1/FVC ratio was calculated for the Hankinson and Crapo reference values. Results: The number of studies interpreted as obstructed varied from 37% using the Hankinson data set to 55% using the 75% fixed ratio method. Comparing the LLN method vs. the 70% fixed ratio method resulted in 7.5% (Hankinson LLN vs. 70% fixed) and 6.9% (Crapo LLN vs. 70% fixed), which were discordant results. Age was the strongest predictor of discordance, and 16% of subjects > 74 years of age had discordant results comparing Hankinson values to the 70% fixed method. Conclusion: At the extremes of age and height, a large number of spirometry test results will be interpreted as showing an obstructive defect if a 70% fixed ratio method is used for interpretation compared with the LLN derived from the Hankinson data set. PMID: 16840402 [PubMed—indexed for MEDLINE].
Comments: There are several reference data sets available for PFT interpretation, and there is no consensus on what is the best data set to use by large private and academic medical centers. Many highly reputable institutions still use older, smaller data sets compared to the Hankinson data set that is derived from the Third National Health and Nutrition Examination Study (NHANES) data set. The ATS/ERS consensus statement on PFT interpretation recommends the use of the Hankinson data set and recommends using the lower (LLN) for the FEV1/FVC rather than the fixed ratio of 70 or 75%, yet it is not widely used currently, and there has been little published to provide evidence that it is of any significant clinical benefit. This paper provides a comparison of several data sets in terms of not only the FEV1/FVC ratio but also in terms of (GOLD) severity classification based on percent predicted FEV1 comparing the Hankinson data set to others. The paper demonstrates the limitations of using the fixed ratio to determine obstruction at extremes of age and height while also examining other variables such as race, gender, and weight. Considering that there are 14–18 million COPD patients who have been diagnosed and perhaps almost as many who have not yet been diagnosed, a rate of 7.5 discordance is not insignificant.
Providing Patients with Reviews of Evidence about COPD Treatments: A Controlled Trial of Outcomes. M. Harris, B. J. Smith, A. Veale, A. Esterman, P. A. Frith, P. Selim (Chron Respir Dis. 2006; 3(3):133–140).
Abstract: Studies in many countries have identified gaps between what is known from research evidence and what is done in clinical practice. Merely making research evidence available to practitioners does not cause much change in their behavior, and researchers are now looking for more effective ways to improve the implementation of evidence. We report outcomes at 3 months of a parallel group trial of an evidence-based patient manual designed to improve implementation of evidence by the patients' doctors. The patient manual was produced with extensive patient and professional input. It contained summaries of the evidence for treatments used in COPD (chronic obstructive pulmonary disease) and prompted discussion of evidence with doctors. Participants in the intervention arm of the trial (n = 125) were supplied with the manual, and participants in the control arm (n = 124) were supplied with a pamphlet about COPD produced by the Australian Lung Foundation. The primary outcome measure (rates of current influenza vaccination and bone density testing) was an indicator of evidence-based management of COPD. Secondary outcomes were quality of life (mastery component), satisfaction with information, communication with usual doctor, and anxiety. At 3 months, no pattern of benefit in outcome measures was found for either group. Process measures showed high levels of personal use of the manual but progression to conversations with doctors for fewer than half of participants and little treatment change. The findings highlight the difficulties of promoting changes in health behavior and show that even when all stakeholders are consulted, success is not guaranteed. Further research is required to identify those patients most likely to use manuals such as the one reported here, and how to make patient mediated interventions more effective for a greater proportion of the target population. PMID: 16916007 [PubMed—in process].
Comments: With the increased interest in COPD and the development of multi-disciplinary COPD sub-specialty clinics the results of this study are somewhat sobering. Nonetheless, one should examine the design and results of such studies to determine what are potential opportunities or options to improve physician and patient behavior and, ultimately, outcomes.