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Bronchial challenge with formaldehyde gas: lack of bronchoconstriction in 13 patients suspected of having formaldehyde-induced asthma.

We studied 13 selected patients with symptoms suggestive of asthma who suspected exposure to formaldehyde as a cause. These patients had a history of exposure to formaldehyde gas which either coincided with the onset of or aggravated their symptoms of asthma. The levels of exposure at their homes or at work ranged from 0.1 to 1.2 parts per million (ppm) of formaldehyde gas. The patients were tested with bronchial challenges of 0.1-, 1-, and 3-ppm concentrations of formaldehyde gas and randomly interspersed room-air placebos. The formaldehyde gas or placebo was delivered via a Dynacalibrator . The period of exposure to formaldehyde gas or placebo with each challenge was 20 minutes. Pulmonary function was measured before and for 24 hours after each bronchial challenge. No patient had a significantly greater decrease in the forced expiratory volume in 1 second after exposure to formaldehyde than after exposure to air. In no case were we able to substantiate that exposure to formaldehyde gas (3 ppm or less) was indeed causing or aggravating the asthmatic symptoms.

Adolescent↗

A prospective study of airway reactivity before bone marrow transplantation.

The purposes of this study were to assess baseline airway function and to determine the frequency of airway reactivity in patients before bone marrow transplantation (BMT). The ratio of the forced expiratory volume at 1 second to the forced vital capacity (FEV1/FVC) was the measure of baseline airflow. Using methacholine challenge, we tested 53 patients before conditioning chemotherapy, total-body irradiation, and BMT. All patients had a baseline FEV1/FVC of 70% or more. The mean baseline FEV1/FVC was 84(+)/- 6%. The response to methacholine challenge was defined by the change in FEV1 from baseline (delta FEV1). A positive response (delta FEV1 of 20% or more) occurred in 11 of 53 patients (21%), a borderline response of (delta FV1 of less than 20% but greater than or equal to 10%) was was found in 10 (19%), and no response (Delta FEV1 of less than 10%) was elicited in 32 (60%). In our group of patients with a positive or borderline response to methacholine, we found no significant relationship to baseline FEV1/FVC, smoking history, hematologic diagnosis or study, or major post-BMT pulmonary complications including bronchiolitis obliterans. We concluded that pretransplantation airway reactivity, as measured by methacholine challenge and in the setting of normal baseline FEV1/FVC, was common before BMT. The presence of a borderline or positive response to methacholine challenge before transplantation was not associated with the development of either clinical or pathologically proven posttransplantation bronchiolitis obliterans.

Adolescent↗

Respiratory impedance in normal humans: effects of bronchodilatation and bronchoconstriction.

Total respiratory resistance and reactance from 3 to 30 Hz were determined by the method of forced random noise oscillation in 12 normal male subjects before and after bronchodilatation and bronchoconstriction induced by deep breaths of aerosols of isoproterenol and atropine and of methacholine and histamine. Isoproterenol and atropine induced small decreases in total respiratory resistance at most frequencies, and isoproterenol decreased resonant frequency slightly (P less than 0.01). After administration of both methacholine and histamine, resonance frequency increased (P less than 0.01) and total respiratory resistance became more frequency-dependent, increasing mainly in the lower frequency range. In six of the subjects, we attempted to produce central deposition of methacholine by rapid, shallow breathing and peripheral deposition of the drug by slow, deep breathing. Only two subjects had suggestive evidence of central bronchoconstriction. No difference was noted, however, in the impedance behavior with either type of breathing. In awake humans, impedance analysis does not seem to distinguish between central and peripheral airway constriction.

Adult↗

The clinical value of pharmacologic bronchoprovocation challenge.

Pharmacologic bronchoprovocation challenge (PBC) can be of considerable clinical value in patients in the pediatric age group and adults because bronchial hyperresponsiveness is present in virtually all symptomatic asthmatics and it can be accurately, reliably, and safely demonstrated by PBC. The principal, proven indication for performing PBC is to rule out or help rule in the diagnostic possibility of asthma as the cause of any unexplained chest complaints in patients with normal or near normal spirometric values.

Asthma↗

Persistence of increased nonspecific bronchial reactivity in allergic children and adolescents.

Nonspecific bronchial reactivity (BR) is commonly associated with asthma. It can be found, however, in subjects with allergic rhinitis. Studies have not been done looking at changes in nonspecific BR in allergic children over time. Therefore, we report on our longitudinal study of BR in allergic children and adolescents. The reported subjects are part of a larger ongoing study in a selected population of families with asthma and of twins. Initiated in 1972, the subjects reported in this study are subjects who have had at least one follow-up visit through 1989 and did not have asthma, but had allergic histories at either their initial visit or follow-up visits. Subjects completed a questionnaire, had skin tests, determination of a serum IgE level, and a determination of nonspecific BR with a methacholine challenge. Subjects were 6 years of age or older or 21 years of age or younger at initial visit. Subjects from families with asthma (N = 76; mean age, 12.09 years; +/- 4.6 SD) and twins (N = 36; mean age, 11.81 years; +/- 3.81 SD) were followed longitudinally, and their age at follow-up visits was not restricted. In this study we observed that, of 106 subjects, 66% initially demonstrated nonspecific BR. At their first and second follow-up visits, 70.4% and 61.3% demonstrated persistence of their BR. These data demonstrate that allergic children and adolescents have increased nonspecific BR. There was not a significant loss of BR over time in the studied subjects.

Adolescent↗

Occupational challenge studies with laboratory workers allergic to rats.

To relate airborne Rat N I concentrations to airway responses in allergic laboratory workers, we collected allergen on personal monitors while workers and control subjects were exposed in a rat vivarium for 1 hour. Allergen concentrations ranged from less than 1.5 to 310 ng/m3 and were significantly (p less than 0.001) higher during cage cleaning (19 to 310 ng/m3) than during quiet activity (less than 1.5 to 9.7 ng/m3). Among 12 rat-allergic volunteers, all had a nasal response during the exposure with an increase in nasal lavage histamine concentrations or TAME-esterase activity, but only five volunteers had a lower respiratory tract response (fall in FEV1 greater than 10%). Two of five allergic control subjects had a small change in nasal TAME-esterase activity, and none had a 10% fall in FEV1. A dose response was demonstrated between the allergen concentrations and the intensity of the nasal allergic response. This occupational challenge procedure thus was able to measure the nasal and lower respiratory tract response to airborne allergen exposure in a work environment. It can be used to define further the determinants of this response.

Adolescent↗

Normal responsiveness of superficial hand veins to alpha- and beta-adrenergic stimuli in allergic asthma: effects of terbutaline and prednisolone on beta-adrenergic responsiveness.

Impaired function of the adrenergic-receptor system has been postulated to contribute to the pathogenesis of bronchial asthma. Using the dorsal hand-vein compliance technique, we compared the changes in diameter of superficial hand veins in response to phenylephrine, an alpha-adrenoceptor agonist, and to isoproterenol, a beta-adrenoceptor agonist, in 14 untreated patients with allergic asthma and in 16 nonatopic control subjects. There were no significant differences in the median effective dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) or in the maximal response (Emax) between the two groups. Bronchial hyperreactivity (assessed by methacholine-challenge tests) in the patients with asthma was uncorrelated with the ED50 or Emax of isoproterenol. These results demonstrate no evidence for a generalized change in alpha- or beta-adrenergic responsiveness on smooth muscle cells in asthma. Hand-vein responsiveness to isoproterenol was unchanged after treatment for 7 days with oral terbutaline (5 mg three times per day). Thus, unlike leukocytes, smooth muscle appears not readily susceptible to beta-adrenoceptor desensitization in vivo. Local infusions of prednisolone or dexamethasone during 2 hours and systemic administration of dexamethasone (24 hours) caused a significant fall in the Emax for isoproterenol. The mechanism of attenuation of beta-adrenoceptor responsiveness by corticosteroids remains to be determined.

Adrenergic alpha-Antagonists↗

Identification of a new physically induced urticaria: cold-induced cholinergic urticaria.

Four patients with symptoms suggestive of either cold urticaria or a combination of cold and cholinergic urticaria were studied. However, all patients were negative to an ice-cube test or cold-immersion test and had no urticaria after exercise in a warm environment. When each patient was seated in a cold room (4 degree C) for 5 to 15 min, generalized urticaria appeared, consisting of puncture wheals and surrounding erythema as seen in cholinergic urticaria. Two patients had weakly positive methacholine skin tests and the other two had completely negative tests. When serial venous blood samples were obtained to test for mediator release, three of four patients had evidence of histamine release and the time course was similar to that previously reported for patients with cholinergic urticaria. These four cases represent a new syndrome with features suggestive of cold and/or cholinergic urticaria, but the results of all the tests usually utilized to diagnose these conditions were negative. We have called this disorder cold-induced cholinergic urticaria to indicate that it is cold dependent and visually indistinguishable from cholinergic urticaria.

Adolescent↗

Elevated mononuclear leukocyte phosphodiesterase in allergic dogs with and without airway hyperresponsiveness.

To investigate if mononuclear leukocyte beta-adrenergic hyporesponsiveness of Basenji greyhound (BG) dogs is associated with atopy or nonspecific airway hyperresponsiveness, we examined the relationship between mononuclear leukocyte cAMP phosphodiesterase levels, airway responsiveness to methacholine, and intradermal allergen responses in 17 BG dogs, five unrelated purebred Basenjis, and five greyhounds. BG dogs were hyperresponsive to aerosols of methacholine compared to Basenjis and greyhounds. Both BG dogs and Basenjis were allergic and had increased leukocyte cAMP phosphodiesterase activity compared to greyhounds. We concluded that the leukocyte abnormality is not associated with airway hyperresponsiveness. The leukocyte abnormality is either associated with the allergic state, with some hereditary trait that BG dogs acquired from the Basenji ancestry, or the leukocyte abnormality is necessary but not sufficient for the development of airway hyperresponsiveness.

3',5'-Cyclic-AMP Phosphodiesterases↗

Methacholine responsiveness increases after ultrasonically nebulized water but not after ultrasonically nebulized hypertonic saline in patients with asthma.

Airway obstruction can be induced in patients with asthma by the inhalation of ultrasonically nebulized aerosols of nonisotonic solutions. It is the change in osmolarity of the periciliary fluid that is believed to be the stimulus for bronchoconstriction. However, it is not known whether hyperosmolar and hypo-osmolar aerosols induce asthma via the same mechanism. We have previously reported that patients with asthma have a reduction in the dose of provoking agent that induces a 20% fall in FEV1 (PD20) for methacholine after challenge with nebulized water. To determine whether hyperosmolar aerosols also increase sensitivity to methacholine, we studied 13 subjects with asthma on 3 days. On day 1, the PD20 to methacholine was determined. On day 2, a challenge with nebulized 4.5% saline was followed by a challenge with methacholine 40 to 60 minutes later. On day 3, a challenge with nebulized water was followed by a methacholine challenge. Sensitivity to methacholine was significantly increased after water (p less than 0.02) but not after 4.5% saline. Furthermore, there was no relationship between the PD20 to water and to 4.5% saline. When the Spearman's correlation coefficient was used to compare sensitivity to the challenges, there was a significant relationship between the PD20 to 4.5% saline and methacholine (p less than 0.01) but not between the PD20 to water and methacholine. These results suggest that the mechanism of asthma induced by hyperosmolar and hypo-osmolar solutions is different.

Adolescent↗

Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma.

Airway inflammation is assumed to be an important determinant in increased bronchial responsiveness (BR). We tested the hypothesis that treatment with an inhaled anti-inflammatory drug (i.e., budesonide) but not with an inhaled beta-agonist (i.e., terbutaline) would reduce BR in children with asthma and with minimal or no bronchoconstriction. Twelve patients were treated with budesonide and seven with terbutaline for 6 months. BR decreased in 11 patients receiving budesonide and was significant in seven patients. BR decreased in none of the patients receiving terbutaline. FEV1 demonstrated a small increase with budesonide but remained unchanged with terbutaline. Except in one patient who received terbutaline, the clinical effect was good. We conclude that inhaled corticosteroids but not inhaled beta-agonists will decrease persistent BR in most children with asthma.

Administration, Inhalation↗

Cromolyn sodium inhibits the increased responsiveness to methacholine that follows ultrasonically nebulized water challenge in patients with asthma.

We have previously reported that airway responsiveness to inhaled methacholine in subjects with asthma is increased 40 to 60 minutes after challenge with ultrasonically nebulized water. This study reveals that increased responsiveness to methacholine is abolished by administration of cromolyn sodium before the water challenge. The mean dose of methacholine (95% confidence limits) inducing a 20% fall in FEV1 (PD20) was 1.10 mumol (0.43 to 2.80). The PD20 after water challenge was 0.42 mumol (0.17 to 1.01) that was significantly lower (p less than 0.005) than that observed for the initial challenge. Administration of cromolyn before the water challenge abolished this increased responsiveness to methacholine. The mean PD20 was 1.32 mumol (0.47 to 3.68) that was not significantly different from that measured for the initial methacholine challenge. Methacholine responsiveness was unchanged when challenge was performed 40 to 60 minutes after cromolyn alone or after methacholine itself. We conclude that cromolyn abolishes the increased responsiveness to methacholine and probably does so by inhibiting the release of mediators.

Adult↗

Achalasia.

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Aged↗