Bronchial reactivity, lung function, and serum immunoglobulin E in smoking-discordant monozygotic twins

Smokers with chronic bronchitis and/or chronic obstructive pulmonary disease (COPD) have been reported to have an increased bronchial reactivity (BR). It has been discussed whether increased BR is a risk factor for the development of COPD in smokers. We studied 10 monozygotic twin pairs who were discordant for tobacco smoking by means of histamine provocation tests, lung function tests, and serum samples for total IgE. The smokers had a mild obstructive ventilatory impairment, with FEV1 significantly lower than that of the partner both when it was determined from the flow-volume loops (3.2 +/- 1.0 L for smokers and 3.4 +/- 0.8 L for nonsmokers) and by the Vitalograph spirometer (3.5 +/- 1.0 L for smokers and 3.8 +/- 0.8 L for nonsmokers). Forced midexpiratory flow (FEF25-75%) and forced expiratory flow at 75 to 85% of vital capacity (FEF75-85%) were both significantly lower in the smokers (p < 0.05). The alveolar plateau phase N2-delta test and lung clearing index in the multibreath nitrogen washout test were both significantly affected in the smokers (p < 0.05 and p < 0.01, respectively). We found no significant difference in histamine reactivity between smokers and nonsmokers and no correlation between differences in reactivity and differences in lung function within pairs. Total serum IgE was significantly higher in the smokers than in their nonsmoking siblings. These data suggest that obstructive ventilatory impairment and raised serum IgE are earlier and more constant manifestations of tobacco smoking than increased bronchial reactivity. Thus, bronchial hyperreactivity does not seem to be a major risk factor for the development of early airways obstruction in smokers.     

Effects of acute and chronic exposure to nicotine aerosol on bronchial reactivity to inhaled methacholine

Normal baboons, like humans, demonstrate a wide range of bronchial reactivity to inhaled methacholine. Cigarette-smoking baboons demonstrate reduced bronchial reactivity to inhaled methacholine compared with sham-smoking controls after 6 pack-yr of smoking. To evaluate the role of nicotine in this blunting of airway reactivity, we studied the effects of both acute and chronic nicotine inhalation on reactivity to methacholine in baboons. Inhalation of 2 mg of nicotine had no acute effect on lung function but blunted bronchial reactivity in highly reactive animals. This effect was not diminished after daily inhalation of nicotine for 90 days. Marked interindividual differences in bronchial reactivity to methacholine were not abolished by propranolol, suggesting that factors other than beta-adrenergic tone account for this intersubject variability.     

Bronchial obstruction and exhaled nitric oxide response during exercise in cold air

This study examines whether exhausting exercise in cold air induces bronchial obstruction and changes in exhaled [NO] and in exhaled NO output (V'NO). Thus, eight well-trained males performed two incremental exercise tests until exhaustion, followed by 5 min of recovery in temperate (22 degrees C) and cold (-10 degrees C) environments, at random. At -10 degrees C, they were dressed in warm clothes. Ventilation (V'E), oxygen consumption (V'O2), carbon dioxide production, cardiac frequency (fC), and [NO] and V'NO were measured continuously. Before and after each test, the subjects' maximal expiratory flow-volume curves and peak expiratory flow, forced expiratory volume in one second (FEV1) and forced expiratory flow at 25 (FEF25), 50 (FEF50) and 75% (FEF75) of forced vital capacity were determined. At -10 degrees C, significant decreases in FEV1 and FEF75 were observed after exercise. At rest and at the same submaximal intensity, V'O2, V'E and fC did not differ significantly. At rest and up to approximately 50% peak V'O2, [NO] and V'NO values were lower at -10 degrees C than at 22 degrees C. Thereafter, and during recovery, the V'NO response became similar at both -10 and 22 degrees C. This study confirms that considerable hyperpnoea in cold air causes a detectable airway obstruction. This airway cooling also induces an initial decrease in the exhaled NO response. Since endogenous NO-production is involved in bronchial dilation, it cannot be excluded that this lack of production may favour the appearance of airway obstruction.     

Mode of action of iron(III) chelators as antimalarials. III. Overadditive effects in the combined action of hydroxamate-based agents on in vitro growth of Plasmodium falciparum

Recent studies suggest a significant contribution of the pulmonary circulation to the perfusion of large airways. In this study we used anesthetized ventilated sheep (n = 19) to determine the functional contribution of the pulmonary circulation to airway smooth muscle. We performed sequential intravenous challenge with methacholine chloride (MCh; 0.25-2.5 mg/ml) to determine airway resistance (Raw) changes in the intact animal, after bronchial artery cannulation that essentially removed bronchial arterial delivery of MCh, and in an isolated lung preparation. After blocking the vagal reflex component of this response, we found that intravenous MCh in the intact preparation resulted in an average 2.2 +/- 0.5 cmH2O.l-1.s increase (181%) in Raw. After prevention of bronchial arterial delivery of MCh, Raw increased by 0.8 +/- 0.3 cmH2O.l-1.s (64%; P < 0.01 compared with intact preparation). In the isolated lung preparation, Raw increased by 0.6 +/- 0.2 cmH2O.l-1.s (63%; P < 0.01 compared with intact preparation). These results demonstrate that in sheep, the bronchial artery provides the major route for delivery of intravenously administered agonists to airway smooth muscle. Considering the large dilutional effect of an intravenously administered agonist by the time it reaches the bronchial artery, we conclude that the pulmonary component of agonist delivery to large airways is < 10% and unlikely to play a major physiological role.     

Assessing the effect of deep inhalation on airway calibre: a novel approach to lung function in bronchial asthma and COPD

Bronchoconstriction in bronchial asthma and chronic obstructive pulmonary disease (COPD) may be due to decreased airway calibre and/or to the inability of the airways to distend after a deep inhalation (DI). The purpose of this review is to discuss the physiological and clinical relevance of this latter mechanism. During induced constriction, DI shows remarkable bronchodilatation in normal subjects, but a blunted or null effect in asthmatics. In contrast, during spontaneous bronchospasm DI tends to decrease airway calibre. From a functional point of view, airway inflammation, remodelling, and peripheral bronchoconstriction could prevent airway smooth muscle from stretching. Therapeutic intervention improving lung function may change the response to DI. For example, bronchodilators allow expiratory airflow before DI to increase more than after DI, because of decreased bronchial hysteresis. This suggest that bronchodilation might be systematically underestimated from parameters derived from maximal expiratory manoeuvres. Inhaled corticosteroids tend to increase the dilator effect of DI, likely due to decreased bronchial and peribronchial oedema. In conclusion, measuring the effects of deep inhalation on lung function is an easy and simple test able to evaluate the structural changes occurring in the airways and to monitor the effectiveness of therapy.     

Certification and occupational health nursing. An historical perspective

BACKGROUND: The bronchodilator agent is an important drug for patients with chronic obstructive pulmonary disease. Methacholine is a popular bronchial provocative agent. Although the major acting site of bronchodilator, methacholine and upper respiratory tract infection (URI) has been evaluated in some studies, the sites are still in debate. This study investigated the exact major acting sites. METHODS: Thirty subjects participated in this study. Episodes of URI were identified by a questionnaire. Spirometry, bronchial provocative test with methacholine, and five minutes' inhalation of a mixture of helium and oxygen (HeO2) were done on day one. Spirometry, bronchodilator test, with five minutes' inhalation of HeO2 and expiratory flow-volume (F-V) curve were performed on another day. The change of pre- and post-HeO2 VEMax50 was calculated as delta VEMax50. The pre- and post-bronchodilator VEMax50 and delta VEMax50 differences were counted to decide the acting site of bronchodilator. After bronchial provocative test with methacholine, the volume of isoflow (VisoV) was estimated from pre- and post-HeO2 F-V curve to establish the acting site of methacholine. RESULTS: This study indicated that small airways are the major acting sites of bronchodilators, large airways are the major acting sites of methacholine and URI affects mainly large airways. Although airway hyperresponsiveness is more severe in subjects with positive methacholine response, the recovery of spirometry values is not significantly different between the methacholine-positive and -negative groups. CONCLUSIONS: The major acting sites of the bronchodilator, methacholine, and URI are the small, large and large airways, respectively. Bronchial hyperresponsiveness is not a cause of quick restoration of spirometry values in subjects with positive methacholine response.     

Bronchial adenoma resection with relief of hypoxic pulmonary vasoconstriction

Experimental airway obstruction is known to cause reflex pulmonary artery constriction, but clinical documentation of reversible bronchial obstruction and vasoconstriction is rare. A soft bronchial adenoma obstructed the left main bronchus, and scans showed minimal ventilation and perfusion on the left. Gas aspirated from beyond the tumor was hypoxic. The adenoma was removed and the lung left intact by means of a skin graft in the bronchial wall. Four months later, pulmonary function was normal, and both ventilation and perfusion of the left lung were normal. Reflex pulmonary vasoconstriction resulting from alveolar hypoxia minimizes systemic hypoxemia and also minimizes alveolar tissue hypoxia in the lung itself. The reflex is seen most frequently in perfusion scans in patients with chronic airways disease. This case in important in that it documents reversal of vasoconstriction after ventilation was restored.     

Radionuclide imaging of airway obstruction following assisted ventilation

Radioaerosol lung scintigraphy was performed in five infants in whom obstructive airway complications developed following assisted ventilation. These studies suggest that a primary functional defect was obstruction to airflow at the level of the major airways, which occurred during expiration. Perfusion lung scintigraphy showed areas of diminished or redistributed pulmonary blood flow, which, like the results of the radioaerosol scintigraphic studies, are findings often associated with adult chronic obstructive pulmonary disease.     

Patterns in children''s fruit and vegetable consumption by meal and day of the week

Seasonal bronchial asthma causally connected with the exposure to pollen allergens is a chronic, eosinophilic mucosal inflammation of airway. This inflammation is the basis for the development of nonspecific bronchial hyperreactivity which is the most typical but mutable feature of asthma. Bronchial hyperreactivity often determines asthma intensity and the need of asthma treatment. The nonspecific bronchial hyperreactivity over two consecutive years was evaluated in 11 patients (2 women and 9 men) with seasonal bronchial asthma, sensitized to grass, remaining under the conditions of natural allergen exposure and out of this period. Bronchial reactivity to histamine was measured by Cockcroft's at all method. So called histamine threshold (PC20H) in mg/ml was assessed. The values of ventilatory parameters (FVC, FEV1) and asthma symptom scores were also measured. It was showed that nonspecific bronchial hyperreactivity significantly increased in subjects with seasonal bronchial asthma during natural pollen exposure. PC20H in two studies performed during this period decreased 3 and 6 times when compared to preseasonal values. The majority part of patients (80%) has the increased bronchial reactivity to histamine also beyond the of grass season when clinical symptoms of asthma and rhinitis are not observed. This postseasonal hyperreactivity could be the effect of the chronic inflammation process persisted from the period of natural allergen exposure. Continuous subthreshold, which means asymptomatic exposure to perennial allergens to which most of patients are sensitized, could be another reason of this hyperreastivity. The possibility of exposure to the activity of seasonal allergens the whole year in persons with asthma can not omitted, as the presence of pollens in the sample of the house dust in patient's flat is observed during the yield of pollen season. Nonspecific bronchial hyperreactivity in individual patients is fluctuated, which probably is not dependent on the intensity of natural allergen exposure.     

Neutral endopeptidase inhibition with inhaled phosphoramidon: no effect on bronchial responsiveness to adenosine 5'-monophosphate (AMP) in asthma

Part of the contractile response of adenosine in the asthmatic airways may be due to the activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides. At present, little is known about the potential role of lung peptidases in modulating adenosine-induced airway dysfunction in humans in vivo. We have, therefore, investigated the change in bronchial reactivity to adenosine 5'-monophosphate (AMP), after treatment with inhaled phosphoramidon, a potent neutral endopeptidase (NEP) inhibitor, in a double-blind, placebo-controlled, randomized study of 12 asthmatic subjects. Subjects attended on six separate occasions, during which concentration response studies with inhaled AMP and methacholine were carried out, initially in the absence of treatment and then after nebulized phosphoramidon sodium salt (10[-5] M) or matched placebo 5 min prior to a bronchoprovocation test with AMP or methacholine. Agonist responsiveness was expressed as the provocative concentration of AMP or methacholine producing a 20% fall in FEV1 from baseline (PC[20,AMP] or PC[20,meth], respectively). When compared to placebo, phosphoramidon failed to potentiate the airway response to AMP. The geometric mean (range) PC20 AMP value of 23.4 (4.4-190.6) mg x mL(-1) after placebo was not significantly different from that of 20.7 (45-100.9) mg x mL(-1) obtained after phosphoramidon. The lack of change in bronchial reactivity to adenosine 5'-monophosphate after phosphoramidon indicates that endogenous airway neutral endopeptidase may not be of physiological importance in modulating the contractile response of adenosine in the airways. Thus, the present data do not support the view that activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides is important in the airway response to adenosine     

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part I: Variability of pulmonary function measures

The acute and subacute effects of ambient concentrations of ozone on lung function have been studied extensively in a variety of settings. Such studies generally have focused on measures of function that reflect either lung volumes or flows that are influenced by the physiology of large and small airways (e.g., forced expiratory volume in one second [FEV1). Data from animal studies suggest that the effects of prolonged exposure to elevated ambient concentrations of ozone result in abnormalities in the centriacinar region of the lung; and dosimetry models for humans predict that long-term exposure to ozone could impact the same areas of the human lung. However, alterations in structure at this level of the lung are not well reflected by measuring FEV1 until substantial structural changes have occurred. Measures of the lung function that reflect the functional mechanics of airways smaller than 2 mm in diameter are considered to be more relevant. At least one epidemiologic study has provided evidence that small-airway functions may be relevant to effects of prolonged exposure to environments with high concentrations of oxidants. A considerable body of physiologic data has established that flow rates measured during the terminal portion of a maximum expiratory flow-volume (MEFV) curve are largely governed by airways smaller than 2 mm in diameter A similar interpretation has been given to changes in the slope of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve. Despite the attractiveness of these measures in relation to airway physiology, some data suggest that measurements of flow via the terminal portions of MEFV and SBNW curves have much greater within-subject variability than forced vital capacity (FVC and FEV1. The present study was undertaken as part of a larger feasibility study to develop methods to study the effects of prolonged exposure to elevated ambient ozone levels on lung function in adolescents. A convenience sample of 239 freshmen (ages 16-20 years) entering the University of California, Berkeley were recruited to participate in this protocol. All were lifelong residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were studied on two occasions five to seven days apart. At each test session, subjects performed up to eight forced expiratory maneuvers to produce three acceptable and reproducible MEFV curves by modified American Thoracic Society criteria. Tests of SBNW were then performed on the basis of detailed criteria for validity and reproducibility. Eight attempts to generate three curves were allowed. The delta N2 was obtained by a least-squares regression of nitrogen concentrations between the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and delta N2 were the principal outcomes. Variance components were estimated with a nested random effects model with adjustments for important covariates. The average within-subject coefficients of variation (+/-SD of distribution of means) for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8 (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4 (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/-17.0). The variance attributed to test session was less than 1% for all measures. The percentages of variance due to within-subject variation for each measure (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1 3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested, 234 (97.9%) could provide at least two acceptable MEFV curves, but only 218 (91.2%) could provide at least two acceptable SBNW curves. The results were unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)     

Analysis of ventilation parameters before and after fiber optic bronchoscopy in patients with atopic bronchial asthma and chronic obstructive pulmonary diseases

Bronchial asthma and chronic bronchitis in a stable period of the disease could be an indication for diagnostic bronchofiberoscopy. The aim of the authors of this article is to assess whether bronchoscopy may be safely used either as diagnostic or therapeutic procedure. 21 patients (age 33-46), 13 with atopic bronchial asthma and 8 with COPD took part in this study. The measurements were carried out one day before and 3 hours after the bronchoscopy. The following parameters: Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), Forced Expiratory Flow (FEF25, FEF50, FEF75) and Resistance of Airways (R aw) were taken into consideration. It was shown that bronchofiberoscopy could be performed safely in these patients and did not lead to woersing ventilation parameters. Bronchospasm was not observed during the study. Moreover the increase in FEF50, FEF75 and R aw were observed. This significant decrease of amount of bronchial discharge could serve as an explanation of this phenomenon.     

Optic chiasm astrocytomas of childhood. 1. Long-term follow-up

There are many in vivo animal models for studying airway mucus secretion and hypersecretion, each with advantages and disadvantages. Use of a particular test system will depend upon the aspect of secretion to be modelled. Airway hypersecretory diseases exhibit chronic mucus hypersecretion, of which the clinical impact is predominantly in the distal airways. The majority of documented test preparations study acute secretion, invariably using tracheal preparations, but have been invaluable in elucidating the normal physiology of airway mucus secretion. Chronic models of the hypersecretory state in the distal airways have been developed, but are predominantly histologic in nature (for example quantification of increased goblet cell number). There are few investigations of mucus hypersecretion. Examination of the 'antisecretory' potential of pharmaceutical compounds has been investigated predominantly in chronic histologic models with the drug being given 'prophylactically' rather than 'therapeutically'. Refinement of chronic hypersecretory models should lead to elucidation of the connection between airway irritation, inflammation, MUC gene expression, mucous cell hyperplasia/metaplasia, airway hypersecretion and bronchial hypersecretory disease.     

Ambulatory patient-activated arrhythmia monitoring: comparison of a new wrist-applied monitor with a conventional precordial device

Sensitivity of forced expiratory flow between 25% and 75% of the vital capacity (FEF25-75) in detecting airway obstruction was investigated in 14 children with mild-moderate asthma, allergic to house dust mites, while at high altitude (1756 m). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEF25-75, and peak expiratory flow (PEF) were measured every 2 weeks for 12 weeks (total, 84 measurements). The presence or absence of wheezing at the chest auscultation was ascertained before each test. During the study period, a significant improvement of both mean (SD) FEF25-75 [61 (12)% vs. 68 (11)% of the predicted value, p = 0.005] and PEF [95 (16)% vs. 103 (13)%, p = 0.002] was observed. FEV1 changed only marginally [82 (7)% vs. 86 (6)%, p = 0.05]. Wheezing was present on 12/84 occasions. Wheezing was associated with abnormal FEF25-75 values on most occasions but not with abnormal FEV1 or PEF. FEF25-75 was decreased on 51% of days in which wheezing was absent. FEV1 and PEF were, respectively, normal in 69% (p < 0.0001) and 92% (p < 0.0001) of measurements in which FEF25-75 was abnormal. These results suggest that FEF25-75 may be considered a good indicator of airflow obstruction and a sensitive marker of respiratory improvement in asthmatic children during reduced antigen exposure.     

Effects of extrinsic positive end-expiratory pressure on mechanically ventilated patients with chronic obstructive pulmonary disease and dynamic hyperinflation

OBJECTIVE: To examine the circulatory and respiratory effects of extrinsic positive end-expiratory pressure (PEEPe) in patients with chronic obstructive pulmonary disease (COPD) and dynamic hyperinflation during controlled mechanical ventilation. DESIGN: Different levels of PEEPe were applied randomly in mechanically ventilated patients with COPD and dynamic hyperinflation. SETTING: Respiratory Intensive Care Unit of a University Hospital. PATIENTS: 9 patients with acute respiratory failure and dynamic hyperinflation due to acute exacerbation of COPD. INTERVENTIONS: PEEPe 35%, 58% and 86% of intrinsic PEEP (PEEPi) were applied. MEASUREMENTS AND RESULTS: Using flow-directed pulmonary artery catheters hemodynamic measurements were obtained, while simultaneously lung volumes, airflows and airway pressures were recorded. In order to estimate alveolar pressures (Palv), rapid airway occlusions during passive expiration were also performed. At no level of PEEPe were significant changes in cardiac output, gas exchange variables, dead space, airways inflation resistances and respiratory system static end-inspiratory compliance observed. At high level of PEEPe central venous, mean pulmonary arterial and pulmonary capillary wedge pressures were increased significantly. All but one patient were flow-limited during passive expiration. PEEPe 86% of PEEPi caused a significant increase in end-expiratory lung volume and total PEEP. Iso-volume pressure-flow curves showed volume-dependence expiratory flow limitation in 2 patients, while in 8 patients volume-dependence of critical driving pressure (Palv-mouth pressure) that decreased flows was also observed. CONCLUSIONS: The effects of PEEPe on iso-volume flow and hence on lung mechanics and hemodynamics, depend on many factors, such as airways resistances, lung volumes and airway characteristics, making the patient response to PEEPe unpredictable.     

Differential effects of nasal continuous positive airway pressure on reversible or fixed upper and lower airway obstruction

Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.     

Evaluation of heliox in children hospitalized with acute severe asthma. A randomized crossover trial

STUDY OBJECTIVE: To determine whether breathing a blend of 70% helium:30% oxygen (heliox) would improve pulmonary function, decrease clinical score, and improve the sensation of dyspnea in children hospitalized with acute severe asthma. DESIGN: Prospective, randomized, double-blind, crossover study. SETTING: The inpatient pediatric service of a military, tertiary care, teaching hospital. PATIENTS: Children 5 to 18 years who required hospital admission for treatment of acute asthma. INTERVENTIONS: All patients received 5 mg of nebulized albuterol every 1 to 4 h, with a dose given within 30 min of the start of the study, and IV administered methylprednisolone. Patients breathed heliox and a 30% oxygen-enriched air mixture for 15 min each in random order. MEASUREMENTS AND RESULTS: Clinical score, dyspnea score, oxygen saturation, heart rate, and respiratory rate, followed by FVC, FEV1, peak expiratory flow rate (PEFR), and, mean midexpiratory flow rate (FEF25-75) were obtained at study entry, 15 min after breathing the first gas mixture (heliox or air per randomization), 15 min after breathing the second mixture, and again 15 min after stopping the second gas mixture (study end values). Eleven children were enrolled, and all completed the study. There were no significant differences between study entry and study end spirometric values. Using the paired t test, we found no significant differences between mean values (SD) of FEV1 and FVC obtained while breathing heliox vs air; FEV1-heliox, 53% (18%) of the predicted value; FEV1-air, 52% (16%) of the predicted value (p = 0.36); FVC-heliox, 69% (22%) of the predicted value; and FVC-air, 70% (21%) of the predicted value (p = 0.50). The differences in values for PEFSR and FEF25-75 while breathing heliox vs air were small but did reach statistical significance in favor of heliox: PEFR-heliox, 56% (20%) of the predicted value; PEFR-air, 50% (16%) of the predicted value (p = 0.04); FEF25-75-heliox, 32% (13%) of the predicted value; and FEF25-75-heliox, 29% (11%) of the predicted value (p = 0.006). Heliox had no effect on either clinical or dyspnea scores. CONCLUSION: The short-term inhalation of heliox did not benefit this group of children hospitalized with acute, severe asthma.     

Canine airway responses to acetylcholine, prostaglandin F2alpha, histamine, and serotonin after chronic antigen exposure

Dose-response curves were obtained for aerosols of acetylcholine (ACh), prostaglandin F2alpha (PGF2alpha), histamine (H), and 5-hydroxytryptamine (5-HT) on pulmonary resistance (Rp) and dynamic lung compliance (Cdyn) in Ascaris-hypersensitive dogs. Previously, these animals had been subjected to chronic biweekly "allergic asthmatic" episodes by aerosol administration of Ascaris antigen. When examined either one week before or after antigen provocation the airways were not hyperreactive to ACh, H, or 5-HT but did demonstrate a modest hyperreactivity to PGF2alpha. When aerosol dose-response curves were obtained for these agonists immediately following an "allergic asthmatic" episode, the airways were hyporeactive to PGF2alpha, H, and 5-HT, but not to ACh. Studies with atropine indicated that the hyporeactivity was the result of decreased airway responsiveness to both direct and indirect effect of PGF2alpha and H. It is concluded that, in dogs, chronic antigen challenge is not accompanied by a general increase in airway reactivity to pharmacologic agents.     

Dirofilaria, visceral larva migrans, and tropical pulmonary eosinophilia

Helminthic infections are prevalent worldwide. The intestinal ascarid, Toxocara, the animal filarial parasite, Dirofilaria, and the human filarial parasite, Wuchereria or Brugia, produce an array of pulmonary disease in humans. Infections are common in temperate, tropical, and subtropical regions of the world. Pulmonary dirofilariasis is essentially an asymptomatic disease. Most cases are diagnosed accidentally after thoracotomy for a solitary pulmonary nodule presumed to be lung cancer. Clinical manifestations of toxocariasis or visceral larva migrans (VLM) are the result of allergic and inflammatory responses of the host, and manifest with airway reactivity, acute pneumonia, and persistent eosinophilia. VLM is a self-limited disease and specific treatment is rarely necessary. In acute cases, a short course of steroids reduces morbidity and mortality but preventive measures are more important in curbing toxocara infection. Tropical pulmonary eosinophilia (TPE) is the result of immunologic hyperresponsiveness to the human filarial antigen and eosinophils play a crucial role in its pathogenesis. Airway hyperreactivity, extreme eosinophilia, and pulmonary physiologic impairment are the characteristic features. Treatment of TPE with diethylcarbamazine results in dramatic amelioration of symptoms. However, low grade inflammation persists in a significant number of patients and can lead to chronic interstitial lung disease. Mass treatment of patients in certain endemic areas has been effective in eliminating TPE.     

Occlusion pressure responses in asthma and chronic obstructive pulmonary disease

During CO2 rebreathing we measured ventilation and the pressure generated during the first 0.1 sec of inspiratory effort against a closed airway (P 0.1) in 12 asthmatics during acute exacerbation, 10 normal subjects, and 10 patients with chronic obstructive pulmonary disease. In normal subjects, the ventilatory responst to CO2 correlated with the P 0.1 response measured as delta In P 0.1. Patients with chronic obstructive pulmonary disease showed depressed responses to CO2 in terms of both ventilation and deltaIn P0.1. However, P 0.1 values in the patients with chronic obstructive pulmonary disease were greater than those of the normal subjects when they were compared at an alveolar PCO2 of 60 mm Hg. Asthmatics' responses to CO2 were similar to those of patients with chronic obstructive pulmonary disease. When measured at an alveolar PCO2 of 60 mm Hg, asthmatics' P 0.1 values were greater than those of both normal subjects and patients with chronic obstructive pulmonary disease. As the asthmatics' airway obstruction decreased so did their P 0.1. The asthmatics, and to a lesser extent the patients with chronic obstructive pulmonary disease, demonstrated increased inspiratory muscle activity that could not be explained on the basis of chemical drive or alterations in functional residual capacity. In the case of the asthmatics it was possible that the increased inspiratory muscle activity was a response to airway obstruction.