Respiratory complications of obesity.

Obesity is known to be a major risk factor of a whole range of cardiovascular, metabolic and respiratory disorders. It has been recognised that the pattern of regional fat distribution plays an important role in the pre-disposition of obese subjects to certain obesity-related complications. Derangement of parameters of lung function is determined to a large extent by the quantity and distribution of excess body fat with its potential to interfere with the mechanics of pulmonary physiology. Clinical, laboratory and epidemiological observations have established links between obesity and several breathing problems including obstructive sleep apnoea, obesity hypoventilation syndrome and asthma. However, in many respects, the pathophysiology of these links is not fully explored. In this article, the impact of obesity on pulmonary physiology and its association with the above-mentioned clinical conditions is discussed.

Airway response to inhaled methacholine in normal human subjects.

The individual airway responsiveness to inhaled, nebulized methacholine (MeCh) was estimated in normal volunteers, measuring specific airway conductance (sGAW). The dose of MeCh was increased logarithmically until a 60-65% reduction from baseline sGAW or an asymptotic approach to a maximal response was attained. The concentration of MeCh that caused a 35% reduction in sGAW (PC35), the dose that caused a 62.5% reduction in sGAW, the slope of the straight, central part of the log-dose-response curve (LDRC), the slope of the straight, initial part of the dose-response curve, the maximal response attainable (Emax) and the dose causing a half-maximal response (ED50) were derived. These parameters were transformed as necessary to attain normality of distribution. Relationships between them were examined by measuring the correlations between their transformed values. The ED50 was taken to represent the least biased estimate of the sensitivity to MeCh. The PC35 was the best practical estimate of sensitivity. The Emax was taken to represent the least biased estimate of the reactivity to MeCh. The slope of the LDRC was the best practical estimate of reactivity. The sensitivity and reactivity varied independently in these normal subjects. Each was also independent of the baseline sGAW.

Trials of the bronchodilator activity of the xanthine analogue SDZ MKS 492 in healthy volunteers during a methacholine challenge test.

An approximately steady-state reduction of specific airway conductance was induced in healthy human subjects by means of an individualized inhaled methacholine loading dose followed by a maintenance dose regime. Tested against this background bronchoconstriction, the xanthine analogue SDZ MKS 492, when administered as a single oral dose of 40 mg, showed a significant bronchodilator action, which lasted for up to 5.5 h. Bronchodilatation was not seen after administration of 10 or 20 mg doses. SDZ MKS 492 inhaled as a dry powder had a bronchodilator action that was small, most evident with the 12 mg dose and transient. The peak relief of imposed bronchoconstriction was 29% and the apparent half-time of removal of SDZ MKS 492 from its site of action was 5-6 min. Inhaled SDZ 492 had a bitter taste that was not masked by inclusion of menthol and aspartame in the formulation. The bronchodilatation seen in laboratory animals can also be produced by SDZ MKS 492 in man when administered orally or by inhalation. Its magnitude correlates better with the plasma concentration of parent drug than with that of either of the identified metabolites. Dispositional processes in the lung abbreviate its action after administration by inhalation.

Acute pulmonary edema in Brucella myocarditis and interstitial pneumonitis.

A case of Brucella pneumonitis and myocarditis complicated by acute pulmonary edema is presented. The clinical, laboratory and roentgenographic findings are discussed.