Tiotropium and simplified detection of dynamic hyperinflation.
OBJECTIVE
To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium.


METHODS
IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH.


RESULTS
At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003).


CONCLUSIONS
In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.
Gelb
Arthur F
AF
Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address: afgelb@msn.com.
Taylor
Colleen Flynn
CF
Department of Pharmacy Services, Lakewood Regional Medical Center, Lakewood, CA.
McClean
Patricia A
PA
Faculty of Medicine, University of Toronto, Toronto, ON. Canada.
Shinar
Chris M
CM
Department of Pharmacy Services, Lakewood Regional Medical Center, Lakewood, CA.
Rodrigues
Marcelo T
MT
Faculty of Medicine, University of Toronto, Toronto, ON. Canada.
Gutierrez
Carlos A
CA
Faculty of Medicine, University of Toronto, Toronto, ON. Canada.
Chapman
Kenneth R
KR
Faculty of Medicine, University of Toronto, Toronto, ON. Canada.
Zamel
Noe
N
Faculty of Medicine, University of Toronto, Toronto, ON. Canada.
D000368:Aged; D000420:Albuterol / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D005652:Functional Residual Capacity / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006985:Hyperventilation / Q000503:physiopathology*; D007320:Inspiratory Capacity / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010993:Plethysmography, Whole Body; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012115:Residual Volume / Q000187:drug effects / Q000502:physiology; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D000069447:Tiotropium Bromide; D014109:Total Lung Capacity / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects* / Q000502:physiology
D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000420:Albuterol; D000069447:Tiotropium Bromide