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Acetazolamide and furosemide attenuate asthma induced by hyperventilation of cold, dry air.

We investigated the assumption that the efficacy of inhaled diuretics in asthma is dependent upon inhibition of the Na+/K+/2Cl- cotransporter. We compared the protective effect of acetazolamide, a diuretic without significant effect on the loop cotransporter, with the protection provided by inhaled furosemide in a cold, dry air hyperventilation model of asthma. Seven asthmatic subjects underwent a baseline bronchial challenge and then received a nebulized dose of 80 mg of furosemide or 500 mg of acetazolamide or saline placebo in a randomized, double-blind, placebo-controlled crossover design. Repeat challenges were performed immediately and at 2 and 4 h postnebulization. Acetazolamide caused a 47.2% increase in the amount of cold, dry air required to reduce the FEV1, by 20% (expressed in terms of respiratory heat loss as PD20RHL), from 0.79 multiplied or divided by (x/divided by) 1.13 kcal/min (geometric mean x/divided by geometric SEM) at baseline to 1.17 x/divided by 1.09 kcal/min postnebulization (p < 0.025). Furosemide increased the geometric mean PD20RHL by 53.9%, from 0.86 x/divided by 1.12 kcal/min to 1.33 x/divided by 1.12 kcal/min (p < 0.001). There was no significant change after placebo inhalation (0.81 x/divided by 1.15 kcal/min versus 0.87 x/divided by 1.10 kcal/min, NS). Airway responsiveness had returned to baseline by 2 h postnebulization on all 3 days. Furosemide also caused bronchodilatation, producing a 14.1% rise in the mean FEV1 (p < 0.005 versus prenebulization), whereas neither acetazolamide nor placebo altered airway tone significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

Reactivity to cold-air hyperventilation in normal and in asthmatic children in a survey of 5,697 schoolchildren in southern Bavaria.

The measurement of bronchial hyperreactivity (BHR) may give additional information to questionnaire-based studies of asthma prevalence. It is desirable to have a provocation method with high specificity that avoids the use of pharmacologic provocations in large numbers of healthy children. It was the aim of this study to establish a range of values for responsiveness to cold-air challenge in normal children, to describe its specificity and sensitivity for a diagnosis of asthma in a large unselected sample of schoolchildren in a field study, and to measure factors associated with hyperresponsiveness. All fourth-grade schoolchildren (9 to 11 yr of age) in Munich and several southern Bavarian communities (n = 9,403) were surveyed with a questionnaire (response rate, 87%), baseline lung function, and cold-air hyperventilation challenge (n = 5,697). A diagnosis of asthma was reported in 7.9% of children. In the reference group, the ninety-fifth percentile (%ile) for the change of FEV1 (DFEV1) was -9.0%; the 90%ile was -7.3%. Asymptomatic children fulfilling all criteria for the reference group showed a significantly increased reactivity if they had a family history of asthma (p = 0.038). With a cutoff for DFEV1 of -9.0% or -7.3% the respective sensitivities to "detect" a diagnosis of asthma were 21.6 and 30.7%, and for asthma with symptoms during the previous 12 months it was 26.2 and 35.1%. Reactivity to cold air increased with the number of episodes of asthma in the previous 12 months. In a multiple linear regression model, factors associated with increased reactivity to cold air were diagnosed asthma, hay fever, male sex, younger age, and a positive skin test.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗

Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure.

Periodic breathing with central apneas during sleep is typically triggered by hypocapnia resulting from hyperventilation. We therefore hypothesized that hypocapnia would be an important determinant of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with congestive heart failure (CHF). To test this hypothesis, 24 male patients with CHF underwent overnight polysomnography during which transcutaneous PCO2 (PtcCO2) was measured. Lung to ear circulation time (LECT), derived from an ear oximeter as an estimate of circulatory delay, and CSR-CSA cycle length were determined. Patients were divided into a CSR-CSA group (n = 12, mean +/- SEM of 49.2 +/- 6.3 central apneas and hypopneas per h sleep) and a control group without CSR-CSA (n = 12, 4.9 +/- 0.8 central apneas and hypopneas per h sleep). There were no significant differences in left ventricular ejection fraction, awake PaO2, mean nocturnal SaO2, or LECT between the two groups. In contrast, the awake PaCO2 and mean sleep PtcCO2 were significantly lower in the CSR-CSA group than in the control group (33.0 +/- 1.2 versus 37.5 +/- 1.0 mm Hg, p < 0.01, and 33.2 +/- 1.2 versus 42.5 +/- 1.2 mm Hg, p < 0.0001, respectively). Neither group had significant awake or sleep-related hypoxemia. In addition, CSR-CSA cycle length correlated with LECT (r = 0.939, p < 0.001). We conclude that (1) hypocapnia is an important determinant of CSR-CSA in CHF and (2) circulatory delay plays an important role in determining CSR-CSA cycle length.

Adult↗

Hyperventilation-induced cerebral hypoxia.

Acute respiratory alkalosis decreases cerebral blood flow, increases the affinity of hemoglobin for oxygen, and can result in cerebral hypoxia. This experiment was designed to study this phenomenon in dogs, and to demonstrate the effect of an increased concentration of inspired oxygen. Seven mongrel dogs were anesthetized with pentobarbital and ventilated with a constant volume respirator. A Telfon-coated stainless steel catheter was placed through a craniotomy into the parietal lobe and advanced through the corona radiata to monitor cerebral PO2 and PCO2 with a mass spectrometer. Steady state cerebral and arterial gas tensions were recorded during eucapnic ventilation with air, eucapnic ventilation with 100% oxygen, hypocapnic ventilation with air, and hypocapnic ventilation with 100% oxygen. Decreased cerebral tissue oxygen tension was demonstrated in hypocapnic dogs ventilated with air. When the concentration of inspired oxygen was increased, the relatively small increase in artrial oxygen content was associated with a marked increase in PO2 at the cerebral tissue level. This may be of clinical importance in therapeutic or centrally mediated hyperventilation.

Animals↗

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.

Adolescent↗

Determinants of response to eucapneic hyperventilation with cold air in a population-based study.

A population-based, epidemiologic investigation conducted in children, adolescents, and young adults analyzed the response to eucapneic hyperventilation with cold air as a continuous variable to better define factors that influence the expression of bronchial responsiveness. Among respiratory illness/symptom variables, only the report of asthma or persistent wheeze in the previous year and the report of a respiratory illness that led to activity restriction were significantly associated with response to cold air. Furthermore, a low, prechallenge FEF/FVC ratio was a significant predictor of response, especially among those subjects who reported a respiratory illness that led to activity restriction. This relationship was not observed for a low prechallenge FEF.

Adolescent↗

Hyperventilation test in syndrome X.

The hyperventilation (HV) test has been extensively used in different forms of coronary artery disease. The purpose of this work was to investigate the response to HV in patients with syndrome X and compare HV with exercise (EX) test. The authors studied 20 patients with syndrome X (angina, a positive EX test, and normal coronary angiogram) and 20 healthy subjects who underwent HV and EX tests. In 7 patients, all women, angina and electrocardiographic (ECG) changes occurred during HV but in none of the controls. Patients with syndrome X and controls had a similar rate-pressure product (RPP) at rest and achieved a similar RPP with HV. The RPP achieved with HV in patients with syndrome X without ECG changes was significantly lower, 121.8 +/-29.1(mean +/-SD), than what was achieved by those with changes, 167.9 +/-42.9, P < 0.01. In patients with an abnormal response to HV the RPP at which angina and ECG changes occurred was similar to that where similar changes were observed during EX. There was a significant correlation of the RPPs between the two tests, r=0.82, P < 0.02. In contrast, in patients in whom no angina or ECG changes occurred, the RPP they achieved with HV was significantly lower than the anginal threshold during EX 204 +/- 47.4, P < 0.0001. In conclusion, a significant proportion of patients with syndrome X, mainly women, who achieve a high RPP with HV, develop angina and ECG changes during overbreathing. The close relation between EX and HV RPPs where these changes occur suggests an increased myocardial oxygen demand as the most likely underlying mechanism for this behavior.

Electrocardiography↗

Pubertal status and emotional reactivity to a voluntary hyperventilation challenge predicting panic symptoms and somatic complaints: a laboratory-based multi-informant test.

The main and interactive effects of pubertal status and emotional reactivity to bodily sensations elicited by a voluntary hyperventilation challenge were examined in relation to panic symptoms and self- and parent-reported somatic complaints among 123 (56 females) adolescents between the ages of 12 and 17 years (M(age) = 15.05; SD = 1.50). As expected, after controlling for baseline anxiety, age, and gender, there was a significant interaction between pubertal status and challenge response in predicting the outcome variables. Specifically, adolescents reporting more advanced pubertal status and greater reactivity to the challenge evidenced greater levels of panic symptoms and somatic complaints, whereas pubertal status had relatively less of an effect on these variables among adolescents who did not respond as fearfully to the challenge. Results are discussed in terms of extant theory and research on anxiety vulnerability among adolescents.

Adolescent↗

Hypothalamic-midbrain dysregulation syndrome: hypertension, hyperthermia, hyperventilation, and decerebration.

Certain decerebrate lesions of brain stem or hypothalamus induce pharmacologically reversible hypertension and hyperthermia in animals. We observed three young patients with episodic decerebration, hyperthermia, hypertension, and hyperventilation during recovery from comas of different etiologies. The shared pathology on neurologic examinations and computed tomographic scans was hypothalamic-mesencephalic dysfunction, suggesting a diencephalic-brain-stem disconnection syndrome or brain-stem release mechanism. Propranolol was the most effective drug tested, but only two patients responded, one dramatically. This novel clinical syndrome may have localizing and therapeutic significance in pediatric coma that needs to be further defined in future studies.

Adolescent↗

Positional hyperventilation-induced hypoxaemia in pectus excavatum.

The presented case is of a young male (aged 19 yrs) with a pectus excavatum who showed significant exercise intolerance, despite normal pulmonary function at rest, including carbon monoxide diffusing capacity. Clinical exercise testing led to a strong suspicion of a right-to-left shunt due to an abnormally wide alveolo-arterial oxygen gradient (26.4 kPa) at peak oxygen uptake, with severe arterial hypoxaemia (arterial oxygen tension 12.54 kPa). A right-to-left shunt was confirmed by transoesophageal echocardiography demonstrating a permeable foramen ovale, despite normal right heart pressures. The right-to-left venous flow was mainly dependent on the upright body position and the deep inspiration. Indeed, i.v. dobutamine infusion to selectively affect cardiac output and hyperventilation induced by tidal volume expansion at constant breathing rate in the supine position did not result in arterial oxygen desaturation or shunting. Closure of the foramen ovale through atrial umbrella placement dramatically improved clinical and physiological abnormalities. This observation demonstrates that a hyperventilatory manoeuvre in the upright position is able to detect a permeable foramen ovale favouring flow in the inferior vena cava in the direction of the abnormal pre-existing atrial channel in a patient with a pectus excavatum.

Adult↗

Mucociliary clearance during and after isocapnic hyperventilation with dry air in the presence of frusemide.

We have previously shown that mucociliary clearance (MCC) decreased during and increased after isocapnic hyperventilation (ISH) with dry air, both in asthmatic and healthy subjects. Inhaled frusemide, an inhibitor of the Na+/K+/2Cl- and NaCl co-transporters on the basolateral membrane of the epithelial cell, prevents the airway narrowing provoked by ISH with dry air. The co-transport system controls epithelial cell volume and chloride secretion and, thus, frusemide has the potential to modify the rate of recovery of periciliary fluid volume during and after ISH with dry air, and hence affect MCC. Frusemide also blocks mediator release from mast cells, which may also modify the increase in MCC after ISH. Eleven asthmatic and 11 healthy subjects inhaled frusemide (35.7 +/- 0.44 mg) or its vehicle, from a Fisoneb ultrasonic nebulizer 30 min before ISH with dry air, on two separate occasions. MCC was measured using 99mTc-sulphur colloid and a gamma camera. Frusemide, compared to its vehicle, did not affect MCC during or 45 min after ISH. However, in the presence of frusemide, the onset of the increase of MCC after ISH was significantly delayed for approximately 10 min in the whole right lung (p < 0.002) and central region (p < 0.01) in the asthmatic but not in the healthy subjects. These findings could be explained by frusemide delaying the recovery of the periciliary fluid volume after ISH with dry air and/or interfering with the stimulus that causes the increase in MCC in the asthmatic subjects after ISH.

Adult↗

Physical performance of patients with numerous psychosomatic complaints suggestive of hyperventilation.

In some patients exercise induces numerous complaints which cannot be attributed to an organic disorder, and which are suggestive of hyperventilation. The study was designed to investigate in this type of patient: 1) exercise capacity and muscle force; 2) breathing pattern and symptoms during maximal exercise and recovery; 3) relationships between symptoms and breathing pattern. Twenty-four patients were compared with 20 healthy subjects. They performed a maximal incremental cycle ergometer test and peripheral and respiratory muscle strength were measured. Patients tended to have a decreased exercise capacity and presented with moderately reduced muscle strength. At comparable minute ventilation, breathing frequency was higher (mean: 24 versus 21 per minute) and tidal volume smaller (mean: 1.42 versus 1.67 L). End-tidal partial pressure of carbon dioxide (PET,CO2) was not significantly different. A significant relation was observed between PET,CO2 and respiratory frequency during recovery in patients, suggesting a reduced flexibility of the ventilatory response to exercise. In patients respiratory complaints and paresthesias were weakly correlated to PET,CO2 at moderate exercise. It is suggested that the physical deconditioning observed in those patients is rather a consequence than a cause of the response to exercise. The link between symptoms and breathing pattern might be explained by a psychological conditioning process.

Adult↗

Psychophysiological investigations of patients with unilateral symptoms in the hyperventilation syndrome.

Anxiety states sometimes lead to hyperventilation (HV) which may, in turn, give rise to a variety of physical symptoms. One way in which HV may present is with unilateral somatosensory symptoms, often left-sided. We report nine such cases. The mechanisms of lateralisation was examined using EEG and bilateral somatosensory evoked potentials which were carried out before and after HV. No difference in conduction velocity was found between affected and unaffected arms, but non-specific abnormalities were frequently noted in the EEGs. The results support the role of a central rather than a peripheral mechanism in the production of unilateral symptoms in HV.

Adult↗

Hyperventilation-induced limb shaking TIA in Moyamoya disease.

The authors present a case of hyperventilation-induced left upper limb shaking from an underlying Moyamoya disease. Video EEG monitoring and SPECT study were performed. Leptomeningeal collateral circulation was investigated by conventional angiography and by SPECT study with acetazolamide. Limb shaking in Moyamoya disease may result from a transient hypoperfusion of the contralateral frontoparietal cortex rather than basal ganglia.

Acetazolamide↗

Hyperventilation and 6-hour EEG recording in evaluation of absence seizures.

Seven patients with poorly controlled absence seizures were evaluated clinically and electroencephalographically (EEG) in control and placebo periods and then evaluated after 10 weeks on valproic acid. For analysis of epileptiform activity, 5 minutes of controlled hyperventilation recording was more reliable than 6-hour recording as a predictor of clinical seizure frequency. This apparently paradoxic result can be explained by considering that the number of epileptiform discharges in the EEG is affected by many variables (such as level of consciousness, anxiety, diurnal seizure variation, or blood glucose level) that are difficult to control for prolonged periods.

Electroencephalography↗

Cold air inhalation does not affect the severity of EIB after exercise or eucapnic voluntary hyperventilation.

INTRODUCTION: Exercise-induced bronchoconstriction (EIB) is thought to result from osmotic and thermal events of air conditioning during exercise at high ventilation rates. The purpose of this study was to evaluate lung function after exercise and eucapnic voluntary hyperventilation (EVH) while breathing both room-temperature and cold-temperature dry bottled air. METHODS: Twenty-two subjects were identified as EIB probable by a fall of >or=7% in forced expiratory volume in the first second of exhalation (FEV1) using a 6-min room-temperature EVH challenge (RTEVH; 22.0 degrees C). Subjects then randomly performed three 6-min challenges: cold-temperature EVH (CTEVH; -1 degrees C), room-temperature exercise (RTEX; 22.0 degrees C), and cold-temperature exercise (CTEX; -1 degrees C), with a period of at least 48 h observed between challenges. Spirometry was performed at baseline and at 5, 10, 15, and 20 min postchallenge. RESULTS: Reasonable agreement was found between challenge modes and room-temperature and cold-temperature challenges. Postchallenge percent falls in FEV1 were -15.21, -13.80, -13.12, and -10.69 for RTEVH, CTEVH, RTEX, and CTEX, respectively. RTEVH resulted in a significantly greater percent fall in FEV1 than CTEX (P=0.048); no other differences in FEV1 were observed. CONCLUSION: Similar postchallenge percent falls in FEV1 for room- and cold-temperature EVH and exercise suggest that dryness is essential to test conditions, as cold temperature did not have an additive effect to the EIB response.

Adult↗

Periodic breathing imitating hyperventilation syndrome.

We report a male patient who developed an unusual periodic breathing. At presentation, the differential diagnosis at bedside between Cheyne-Stokes and primary hyperventilation syndrome was laborious, and the final verification was based on the result of capnography.

Cheyne-Stokes Respiration↗