Physiologic correlates of distal lung inflammation in asthma.

BACKGROUND The distal lung is an important site of inflammation in asthma. Maximal midexpiratory flows and the ratio of maximal:partial flows are purported to reflect distal lung function. OBJECTIVE We obtained contemporaneous transbronchial biopsy, spirometry, and plethysmography to describe more accurately the relationship between physiology and distal lung inflammation in asthma. METHODS Ten patients with severe, persistent asthma with mean +/- SE FEV(1) of 2.8 +/- 0.2 L and overnight fall in FEV(1) of 22.8% +/- 3.8% underwent transbronchial biopsy, spirometry, maximal midexpiratory flows, maximal:partial ratio, and lung volumes, all at 4 am. Morphometric analysis was performed after immunohistochemistry for eosinophils, lymphocytes, macrophages, mast cells, and neutrophils. RESULTS Maximal midexpiratory flows, maximal:partial ratio, FEV(1), and forced vital capacity were not significantly correlated with alveolar tissue inflammation. However, the degree of eosinophilic alveolar inflammation was significantly and positively correlated with both total lung capacity (Spearman rho=0.70; P=.03) and thoracic gas volume (rho=0.62; P=.05). Correlation between eosinophils and other lung volumes was not observed. Other inflammatory cell types did not correlate with lung volumes. CONCLUSION Purported physiologic measures of distal lung function are poorly correlated with histopathologic evidence of distal lung inflammation. Measurement of lung volumes more accurately reflects eosinophilic distal lung inflammation.

[1]  P. Howarth,et al.  Immunohistochemistry on resin sections: a comparison of resin embedding techniques for small mucosal biopsies. , 1993, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[2]  E. R. Mcfadden,et al.  A reduction in maximum mid-expiratory flow rate. A spirographic manifestation of small airway disease. , 1972, The American journal of medicine.

[3]  E. Ingenito,et al.  Responsiveness, inflammation, and effects of deep breaths on obstruction in mild asthma. , 1989, Journal of applied physiology.

[4]  A. James,et al.  The structure of large and small airways in nonfatal and fatal asthma. , 1993, The American review of respiratory disease.

[5]  R. Martin,et al.  Distal lung dysfunction at night in nocturnal asthma. , 2001, American journal of respiratory and critical care medicine.

[6]  J. Charpin,et al.  Bronchoconstrictor effects of a deep inspiration in patients with asthma. , 1975, The American review of respiratory disease.

[7]  R. Djukanović,et al.  Alveolar tissue inflammation in asthma. , 1996, American journal of respiratory and critical care medicine.

[8]  W. R. Taylor,et al.  Effects of deep inhalation in asthma: relative airway and parenchymal hysteresis. , 1985, Journal of applied physiology.

[9]  Q. Hamid,et al.  Effect of HFA-flunisolide on peripheral lung inflammation in asthma. , 2003, The Journal of allergy and clinical immunology.

[10]  J. Hogg,et al.  Site and nature of airway obstruction in chronic obstructive lung disease. , 1968, The New England journal of medicine.

[11]  C. Leach,et al.  Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. , 1998, The European respiratory journal.

[12]  P. Thompson,et al.  Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma. , 1999, Chest.

[13]  R. Østerby,et al.  Optimizing sampling efficiency of stereological studies in biology: or ‘Do more less well!‘ , 1981, Journal of microscopy.

[14]  J. Drazen,et al.  Inflammatory cell distribution within and along asthmatic airways. , 1998, American journal of respiratory and critical care medicine.

[15]  Spirometry. FEV1 vs FEF25-75 percent. , 1983, Chest.

[16]  H. Gundersen.  Stereology of arbitrary particles * , 1986, Journal of microscopy.

[17]  V. Howard,et al.  Unbiased Stereology: Three-Dimensional Measurement in Microscopy , 1998 .

[18]  Site and mechanism of obstruction and hyperresponsiveness in asthma. , 1987, The American review of respiratory disease.

[19]  E. Bleecker,et al.  Peripheral lung resistance in normal and asthmatic subjects. , 1990, The American review of respiratory disease.

[20]  E. R. Sutherland,et al.  Distal lung inflammation in asthma. , 2002, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[21]  R. Djukanović,et al.  Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma. , 1999, American journal of respiratory and critical care medicine.