Relative contributions of large and small airways to flow limitation in normal subjects before and after atropine and isoproterenol.

Ingram, R. H.; Wellman, James J.; McFadden, E. R.; Mead, J.

doi:10.1172/jci108688

Cited by 115 publications

(34 citation statements)

References 19 publications

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“…The result was not expected a priori as it is generally thought that ipratropium produces its bronchodilating effect mainly in the central airways [22,23].…”

Section: Discussionmentioning

confidence: 91%

Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium

et al. 2000

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The efficacy and safety of salmeterol alone was compared with the combination of salmeterol plus ipratropium and with placebo during long-term treatment in patients with stable chronic obstructive pulmonary disease. In addition, the single-dose effect in response to the first dose of treatment was studied over 12 h.The patients (n=144; age 64 7 yrs, forced expiratory volume in one second (FEV1) 44 11% pred) participated in a three-centre double-blind double-placebo parallel group study and were randomized after a run-in period of 2 weeks to receive either salmeterol 50 mg b.i.d., salmeterol 5 mg b.i.d. plus ipratropium 40 mg q.i.d. or placebo for a period of 12 weeks.The single-dose study demonstrated that salmeterol produced a significant increase in FEV1 (peak of 7% pred) and specific airway conductance (sGaw) (maximum of 60% baseline) for $12 h. The combination of salmeterol plus ipratropium elicited a greater bronchodilator response (11% and 94% increases respectively) than salmeterol alone during the first 6 h after inhalation. During treatment there were significant improvements in daytime symptom scores and morning peak expiratory flow in both the salmeterol and the salmeterol plus ipratropium groups (p<0.001), with an associated decrease in the use of rescue salbutamol. Improvements in FEV1 and sGaw were greater in the salmeterol plus ipratropium group than in the patients receiving only salmeterol. Thirty-five patients had an exacerbation; 11 (23%) in the salmeterol group (versus placebo NS), six (13%) in the salmeterol plus ipratropium group (versus placebo p<0.01) and 18 (36%) in the placebo group.In conclusion, in patients with severe stable chronic obstructive pulmonary disease, long-term treatment with either salmeterol alone or salmeterol plus ipratropium is safe and effective. There was added benefit from the combination therapy in terms of improvement in airways obstruction, but not for improvement in symptom control or need for rescue salbutamol. Eur Respir J 2000; 15: 878±885. Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by the presence of airflow obstruction, due to chronic bronchitis or emphysema, and is generally progressive but may be partially reversible [1]. The goals of pharmacotherapy in this disorder are to induce bronchodilation and facilitate expectoration in order to improve symptoms, prevent recurrent exacerbations and so enhance the quality of life [2]. In patients with stable COPD, the spirometric response to bronchodilators such as b 2 -agonists, anticholinergic drugs and methylxanthines is at best very modest. However, even in the absence of significant bronchodilation, an improvement in symptoms and exercise tolerance can be demonstrated [3].Salmeterol xinofoate, a long-acting b 2 -agonist, has been shown in single-dose studies to induce a spirometric improvement over a 12-h period in patients with COPD [4± 6]. In addition, three studies in patients with COPD over periods of 1±3 months have found that treatment with salmet...

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“…The result was not expected a priori as it is generally thought that ipratropium produces its bronchodilating effect mainly in the central airways [22,23].…”

Section: Discussionmentioning

confidence: 91%

Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium

et al. 2000

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“…If these chemical mediators were the main substances active in small airway responders, small airway responders in the present study would have been more hyperreactive than the large airway responders. From the analysis of maximal expiratory flow-volume curves with inspired gases of different densities, Ingram et al (1977) suggested that in normal subjects the predominant sites of atropine aerosol activity are the central airways and sites of isoproterenol are the peripheral airways. Later, using the concept that changes in anatomic dead space reflect changes in central airway dimension, Hensley et al (1978) reached the same conclusion.…”

Section: Treatment Of Peripheral Airway Hyperreactivitymentioning

confidence: 99%

Bronchial Hyperreactivity in the Peripheral Airways.

Sasaki

Sekizawa

Yamaya

1995

Tohoku J. Exp. Med.

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“…This finding is compatible with the absence of changes in large airway resistance. This was corroborated functionally by normal values of Raw and SGaw in the diabetic group and reinforced the relative preservation of respiratory muscle function since the determinants of these flows are resistance of large airways and muscle effort (33,34).…”

Section: Discussionmentioning

confidence: 66%

Pulmonary function, cholinergic bronchomotor tone, and cardiac autonomic abnormalities in type 2 diabetic patients

Melo

Vianna

Gallo

et al. 2003

Braz J Med Biol Res

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This prospective study analyzed the involvement of the autonomic nervous system in pulmonary and cardiac function by evaluating cardiovascular reflex and its correlation with pulmonary function abnormalities of type 2 diabetic patients. Diabetic patients (N = 17) and healthy subjects (N = 17) were evaluated by 1) pulmonary function tests including spirometry, He-dilution method, N 2 washout test, and specific airway conductance (SGaw) determined by plethysmography before and after aerosol administration of atropine sulfate, and 2) autonomic cardiovascular activity by the passive tilting test and the magnitude of respiratory sinus arrhythmia (RSA). Basal heart rate was higher in the diabetic group (87.8 ± 11.2 bpm; mean ± SD) than in the control group (72.9 ± 7.8 bpm, P<0.05). The increase of heart rate at 5 s of tilting was 11.8 ± 6.5 bpm in diabetic patients and 17.6 ± 6.2 bpm in the control group (P<0.05). Systemic arterial pressure and RSA analysis did not reveal significant differences between groups. Diabetes intragroup analysis revealed two behaviors: 10 patients with close to normal findings and 7 with significant abnormalities in terms of RSA, with the latter subgroup presenting one or more abnormalities in other tests and clear evidence of cardiovascular autonomic dysfunction. End-expiratory flows were significantly lower in diabetic patients than in the control group (P<0.05). Pulmonary function tests before and after atropine administration demonstrated comparable responses by both groups. Type 2 diabetic patients have cardiac autonomic dysfunction that is not associated with bronchomotor tone alterations, probably reflecting a less severe impairment than that of type 1 diabetes mellitus. Yet, a reduction of end-expiratory flow was detected.

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Relative contributions of large and small airways to flow limitation in normal subjects before and after atropine and isoproterenol.

Cited by 115 publications

References 19 publications

Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium

Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium

Bronchial Hyperreactivity in the Peripheral Airways.

Pulmonary function, cholinergic bronchomotor tone, and cardiac autonomic abnormalities in type 2 diabetic patients

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