Hyperventilation-induced Asthma Research Articles

Duration and magnitude of action of 50 and 100 μg of inhaled salmeterol in protecting against bronchoconstriction induced by hyperventilation of dry cold air in subjects with asthma

Salmeterol is a new long-acting and highly selective &-agonist agent. Clinical studies have shown that it has a very long (at least 12 hours) duration of action in terms of its bronchodilator effect1 and that its effect on bronchial hyperresponsiveness may even be longer. In a recent study we showed that salmeterol administered in a single dose of 50 pg still had a complete blocking effect on hyperventilation-induced asthma in four of 12 subjects (one third) who were tested up to 12 hours later.’ The recommended dose of this preparation varies between 50 and 100 pg every 12 hours. The aim of this study was to expand our previous work on characterizing the magnitude and duration of action of inhaled salmetereol on hyperventilation-induced bronchoconstriction in a more detailed way, especially on the interval between 12 and 24 hours and later after its administration. We also wanted to compare the efficacy of two different doses, 50 and 100 pg. recent modification in their need for a bronchodilator) were included in the study. The project was accepted by a local ethics committee, and a written consent form was obtained from each participant.

Cold and the airways.

Physiological and pathological respiratory responses are triggered by various conditions of exposure to cold climates. Beside airway smooth muscle, both the pulmonary and the tracheobronchial vasculatures are major effectors of respiratory responses to cold. General exposure to cold causes pulmonary vasoconstriction known as "Raynaud's phenomenon of the lung" in subjects with primary Raynaud syndrome and favors acute pulmonary oedema in subjects with congestive heart failure. In healthy subjects acute hyperventilation of very cold air has led to acute respiratory failure closely similar to hypoxic pulmonary oedema. In outdoor exercising people years long repetition of hyperventilation of subfreezing air causes "eskimo lung" made of obstructive lung disease and increased wall thickness of pulmonary arteries. At a lesser degree hyperventilation of dry air cools the central airways and triggers subclinical bronchial obstruction in healthy subjects. In asthmatic subjects hyperventilation of dry air causes asthma attacks. Results of recent animal and human experiments point to a key role of mucosal vessels in thermal balance of the airways. Simultaneously, there is increasing evidence that hyperventilation-induced asthma is triggered by a thermal stimulus.

Comparison of refractoriness after exercise-and hyperventilation-induced asthma

To study the relationship of bronchoconstriction and refractoriness we performed pairs of exercise and hyperventilation tests in 15 patients (mean [SEM] age 28.5 [2.8] years) with a history of exercise-induced asthma. Mean (SEM) maximum specific airway resistance (SRaw) increased during the first exercise test to 33.9 (4.5) and during the second exercise test to 29.8 (5.2) cmH2O x s (n.s.). Mean (SEM) maximum specific airway resistance (SRaw) increased during the first hyperventilation test to 44.0 (5.9) and during the second hyperventilation test to 27.4 (3.3) cmH2O x s (p less than 0.01). Mean maximum bronchoconstriction after corresponding exercise and hyperventilation tests did not differ statistically. There was a significantly larger inter-individual variability in the airway response to hyperventilation (p less than 0.001). From these data we suggest that similar refractoriness can be observed after both exercise and hyperventilation.

The Effect of Body Posture on Exercise- and Hyperventilation-induced Asthma

Recent studies have shown that swimming is of relatively low asthmogenicity, even under conditions of high respiratory heat (and/or water) loss (RHL). It has been suggested that the horizontal body position may contribute to swimming's low asthmogenicity. We studied the effects of upright and prone body postures on pulmonary function following exercise (EIA) and after nonexercise hyperventilation (HIA). Twelve asthmatic boys (aged 12 to 16 years) underwent two 8-min exercise sessions of shoulder flexion-extension and two 8-min isocapnic hyperventilation treatments, in a counterbalanced order, either while lying prone or standing upright. All tests were carried out in a climatic chamber at 10 +/- 1 degree C and 31 +/- 2 percent relative humidity. Minute ventilation (VE) was kept constant at a predetermined individual level during all treatments. No differences were observed in pulmonary functions between the prone and upright postures following either exercise (FEV1 = -20.5 +/- 18.7 percent vs -22.2 +/- 18.7 percent, respectively) or hyperventilation (FEV1 = -29.6 +/- 19.0 percent vs -29.7 +/- 20.2 percent). We conclude that body posture on land has no meaningful effect on the severity of bronchoconstriction in asthmatic children; however, in view of some conceivable physiologic benefits of the prone position in water, an interactive effect on swimming-induced asthma (SIA) of body posture and water immersion cannot be ruled out.

620 Emotional-related hyperventilation-induced asthma in severe asthmatic children

620 Emotional-related hyperventilation-induced asthma in severe asthmatic children

Breathing dry air causes acute epithelial damage and inflammation of the guinea pig trachea.

Drying and cooling of the airways mucosa caused by respiratory water loss may be responsible for exercise- and hyperventilation-induced asthma. Therefore we designed this study to investigate whether breathing dry air is capable of causing structural changes of the airways mucosa. Anesthetized guinea pigs breathed spontaneously through a tracheostomy either dry (n = 15) or water-saturated (n = 12) air at approximately 38 degrees C for 30 or 60 min, during which time total pulmonary resistance (TPR) was measured. Immediately afterward, the animals were killed and the lungs and airways were prepared for histological examination (light microscopy, transmission electron microscopy, and scanning electron microscopy). With dry as well as humid air, there was no change in TPR or in the structure of the main bronchi and lung parenchyma. With humid air the tracheal mucosa was normal in six guinea pigs and exhibited minor changes of the ciliae in eight and localized epithelial damage on light microscopy in the remaining animal. With dry air we found widespread loss of the ciliae on scanning electron microscopy in 10 of 12 animals, associated with detachment or sloughing of the epithelium, subepithelial vascular congestion, edema, and cellular infiltration on light microscopy. Our data demonstrate that a short exposure of the trachea to dry air causes marked epithelial lesions and local inflammation.

Reappraisal of the Refractory Period after Hyperventilation-Induced Asthma

Reappraisal of the Refractory Period after Hyperventilation-Induced Asthma

Neutrophil chemotactic factor in exercise- and hyperventilation-induced asthma.

Elevated levels of the mast-cell-associated serum neutrophil chemotactic factor (NCF) and an increase in blood basophil counts were observed in 6 atopic asthmatics during exercise-induced asthma (EIA). These changes were not found when the same degree of airways obstruction was elicited in the same subjects by isocapnic hyperventilation (ISH) with cold air. The NCF was unlikely to be related to the basophilia alone, because asthmatics without EIA who underwent the same exercise task, produced a similar basophilia but significantly less NCF. These findings suggest that mast-cell-associated (as opposed to basophil-associated) mediators of hypersensitivity are detectable in the bloodstream during the bronchoconstriction induced by exercise, but not by ISH.

Refractory period after hyperventilation-induced asthma.

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%). Because in a previous study it was shown that exercise while breathing warm humid air could induce a refractory period without itself causing asthma, we conclude that hyperventilation-induced asthma is not the same as exercise-induced asthma in most subjects.

Hyperventilation-induced asthma: evidence for two mechanisms.

The mechanism by which airway cooling induces airflow obstruction in asthmatic subjects has not yet been established. Using a pair of isocapnic hyperventilation challenges, with a 40-minute interval, we looked for the presence of a refractory period in 19 asthmatic patients (aged 9-18 years). The subjects fell into two groups. The eight in the "non-refractory" group showed less than a 25% reduction in response to the second challenge, but the 11 in the "refractory" group showed at least a 35% reduction. Twelve subjects also performed a hyperventilation challenge after cholinergic blockade with inhaled ipratropium bromide. In five, in whom no refractoriness after hyperventilation was seen, there was a significant protection from cholinergic blockade (p less than 0.05). In these a vagal (cholinergic) reflex seems likely. The remaining seven, who had a refractory period, received no significant protection from cholinergic blockade and therefore no evidence for the presence of any cholinergic mechanism. We conclude that two mechanisms are responsible for hyperventilation-induced asthma, one of which is a vagal reflex while mediator release may be the other.

Venous plasma histamine in exercise- and hyperventilation-induced asthma in man.

1. Venous plasma histamine was measured by a specific and sensitive radioenzymatic assay in seven male extrinsic asthmatic and six age-matched non-atopic non-asthmatic male subjects during exercise and voluntary isocapnic hyperventilation. 2. There was no change in peak expiratory flow in normal subjects with exercise or hyperventilation, but asthmatic subjects showed a 29.4 +/- SEM 5.8% fall after exercise and a 29.0 +/- 5.4% fall after matched hyperventilation. 3. Plasma histamine was significantly higher (P less than 0.05) in asthmatic (6.2 +/- 0.95 nmol/l) than that in normal subjects (3.4 +/- 0.61 mol/l) and showed a significant (P less than 0.01) rise (to 14.4 +/- 1.83 nmol/l) during exercise in asthmatic, but not in normal subjects. This suggests that discharge of mast-cell mediators may occur during exercise in asthmatic subjects who develop exercise-induced asthma. 4. With hyperventilation there was no change in plasma histamine in either asthmatic or normal subjects, but this does not exclude the possibility that mediators may be released locally in the airways.

Catecholamines in Exercise and Hyperventilation-Induced Asthma

Catecholamines in Exercise and Hyperventilation-Induced Asthma

Exercise-induced asthma.

The effect of exercise on ventilatory function was studied in 7 patients with asthma. Three showed appreciable decrease in forced expiratory volume in one second (FEV 1) after exercise. The degree of hyperventilation produced by exercise correlated with the postexercise decrease in FEV 1. Voluntary hyperventilation at rest produced a decrease in FEV 1 in all patients with asthma. Breathing 5.6 per cent carbon dioxide during voluntary hyperventilation instead of room air induced a larger ventilation and greater decrease in FEV1. Neither exercise nor voluntary hyperventilation had any significant effect on the FEV 1 in normal subjects and patients with chronic bronchitis. Both exercise·induced and hyperventilation-induced decrease in FEV 1 were inhibited by prior administration of isoproterenol but not by atropine. It is postulated that exercise-induced asthma is probably hyperventilation-induced asthma. Several underlying mechanisms by which airway obstruction is produced are possible.