Effect of respiratory training with a mouth-nose-mask in tetraplegics.

Ten tetraplegics, 8 males and 2 females, with a median age of 32 years participated in a scheduled 6 weeks training programme with a respiratory muscle training mouth-nose-mask (RMT-mask) with a fixed expiratory and an increasing inspiratory resistance set by the tetraplegic in accordance to his/her increasing ability during the training period. During the 6 weeks the tetraplegics required to use the RMT-mask for 15 minutes three times a day. Before and after each training session they measured peak flow (PEF). Lung volumes, ventilatory and diffusion capacity were measured before and after the 6 weeks training period. The training resulted only in a significant change in the PEF, which increased with 11% from 371 l/min before to 412 l/min in average after the 6 weeks of training (p less than 0.025). This statistically significant increase was confirmed by the measurements of PEF performed by the tetraplegics themselves during the training period. In addition there was an increase in PEF from before to immediately after each 15 minutes training session, this trend reached statistically significance (p less than 0.025) in the third '2 weeks period'. These results might indicate a possibility of improving the tetraplegics ability to cough by use of a simple RMT-mask, which in turn might prevent certain lung complications including pneumonia, and atelectasia.

A comparative study of the effects of two different doses of nedocromil sodium and placebo given by pressurised aerosol in exercise-induced bronchoconstriction.

Fourteen adult subjects with stable asthma were treated using a double-blind crossover, randomised protocol, with either nedocromil sodium (4 mg or 2 mg) or placebo. The agents were administered from matched pressurised aerosol inhalers 30 min before exposure to an exercise regimen which, on a previous screening day, resulted in a 24-53% (mean: 33.9%) decrease in peak expiratory flow (PEF). Both doses of nedocromil sodium were significantly superior to placebo in preventing the exercise-induced decrease in PEF and were without side effects. This study confirms and extends the results of earlier trials with nedocromil sodium and further supports the contention that this new agent may be of benefit in the treatment of reversible obstructive airways disease in the adult patient.

Ergogenic effect of inhaled beta 2-agonists in asthmatics.

To investigate the effect of beta 2-agonists on exercise performance, eight asthmatics performed an incremental exercise test on a treadmill. Five minutes before the start of the exercise, they were treated with inhaled salbutamol or placebo in a double-blind manner. The exercise started at a low intensity (2 mph, 10% inclination), and every 3 min the speed was increased by 0.5 mph at the same inclination until the subjects were exhausted. Every minute peak expiratory flow, heart rate, blood lactate concentration, and rating of perceived exertion were measured. The same parameters were also measured following the completion of the exercise. No significant difference was seen in total working time, maximal lactate concentration, heart rate, or rating of perceived exertion, whereas the decrease in peak expiratory flow was reduced following pretreatment with salbutamol. It is concluded that the release of inhaled beta 2-agonists for use in competitive events is justified as no ergogenic effect was seen.

Pulmonary function and acid application in the esophagus.

The effect of acid application in the esophagus on pulmonary function was measured in three groups of patients in a double-blind investigation. Group 1 consisted of ten patients with esophagitis but without pulmonary disease, group 2 was 21 patients with bronchial asthma without esophagitis, and group 3 was eight patients with both esophagitis and bronchial asthma. Pulmonary function was assessed by total lung capacity (TLC), airway resistance (Raw), residual volume (RV), and peak expiratory flow (PEF). The four parameters were measured at the following five times during a single trial: before and after insertion of an esophageal catheter; after instillation of 50 ml of isotonic sodium chloride solution; after instillation of 50 ml of 0.1 N hydrochloric acid; and after intravenous injection of atropine (0.01 mg/kg of body weight). A significant decrease (the Wilcoxon test, p less than 0.02; and the Mann-Whitney test, p less than 0.002) in PEF and a significant increase (p less than 0.02 and p less than 0.002, respectively) in Raw after instillation of HCl were seen only in group 3. Changes in the other groups were small and without any regular pattern. Six of the patients in the third group accepted another trial after three days of pretreatment with atropine (0.01 mg/kg twice daily). Now instillation of acid did not produce any change in PEF or Raw (p less than 0.001). We conclude that a modest bronchoconstriction when acid is present in the esophagus is seen in patients with bronchial asthma and severe esophagitis. Atropine inhibits this bronchoconstriction, indicating vagal mediation.

Measurement and regulation of nasal airflow resistance in man.

A method for measuring human nasal airflow resistance (Rnaw) is described. Air flows at constant pressure through both nasal cavities via a face mask and out through the mouth. Airflow is inversely related to Rnaw. The method has several advantages over many other methods for measuring Rnaw, in particular allowing aerodynamic separation of nose and lungs, and frequent measurements over long periods without discomfort to or intervention with subjects or patients. We have used this method to obtain standard values of Rnaw in healthy subjects and in patients with asthma and/or rhinitis. Age has a negative correlation with Rnaw but no sexual difference was seen. Cigarette smoking increases Rnaw especially in young adults. Patients with rhinopathy have much higher resistances than healthy subjects, but those with asthma alone do not. Rnaw is sensitive to changes in ventilation and lung volumes; deep inspiration and oral hyperventilation decrease Rnaw, while deep expiration, nasal hyperventilation and breath-holding increase it. Hypoxia and hypercapnia locally applied in the nose increase Rnaw. It is suggested that these changes are predominantly due to changes in control of the nasal vascular bed.

Effects of pulmonary inhalation of water and histamine aerosols on nasal airflow resistance in man.

We investigated the effect of aerosols inhaled into the lungs on nasal airflow resistance (Rnaw) using a constant inflow pressure method with measured airflow. Isotonic saline and water aerosols produced no immediate significant change in Rnaw and forced expired volume in 1 s (FEV1); however, water gradually decreased FEV1 and increased Rnaw, the response being maximal 10-15 min after provocation. Histamine aerosol significantly increased Rnaw in healthy subjects, asthmatics and asthmatics with allergic rhinitis. There was also a corresponding decrease in FEV1. The increase in Rnaw and the decrease in FEV1 were reversed by inhalation of terbutaline (10 mg . ml-1). Similarly, terbutaline in patients with mild asthmatic attacks decreased Rnaw and increased FEV1. Since terbutaline applied locally into the nose is known to increase Rnaw, we conclude that lung provocation can increase nasal Rnaw, presumably via nervous pathways.

Exercise-induced asthma.

All asthmatics have exercise-induced asthma (EIA). In periods where the asthma spontaneously deteriorate, there will be more exercise-induced asthma. About 3/4 of the asthmatics will have a positive exercise test on the first challenge. Exercise is not the best test to obtain the diagnosis of asthma, as other tests, e.g. inhalation of histamine, is more sensitive and specific. The best pretreatment of EIA is inhaled beta 2-agonists. Inhaled, nebulized SCG seem to offer better protection against EIA than inhalation of SCG as a powder and is most effective in children. EIA should today primarily be used in studies concerning the pathogenesis of asthma and in the evaluation of medication against asthma.

Water loss from the respiratory tract during hyperventilation in normal subjects and in asthmatics.

Expiratory water loss was measured in four asthmatics and in four healthy subjects by leading the expired air through a tube filled with silicagel during hyperventilation. No difference in water loss was seen as the average water loss was 0.025 g/l for the asthmatics and 0.029 g/l for the healthy subjects. After hyperventilation PEF decreased more than 20% in the asthmatics while no change was seen in the lung function of the healthy subjects. It is concluded that expiratory water loss per se is not the reason for the decrease in lung function seen in asthmatics after exercise and hyperventilation.

Isocapnic hyperventilation.

Eucapnic hyperventilation is probably the same expression of asthma as exercise-induced asthma. Some dispute exists about the refractory period after the two challenges. Some claims that an refractory period exists after exercise-induced asthma and some cannot find any refractory period. The changes in the ventilatory capacity of asthmatics following exercise and eucapnic hyperventilation are similar.

Reproducibility of histamine inhalation in asthmatics.

The reproducibility of the changes in FEV, induced by inhalation of histamine, was studied in adult asthmatics. Histamine was inhaled from a Hudson nebulizer, delivering 0.3 ml/min, at tidal breathing through one minute. FEV was measured immediately before and two minutes after cessation of the inhalation. Identical concentrations of histamine were inhaled by the individual patient on every challenge. Reproducibility was studied on the same day, with one day inbetween the histamine challenges and with 12 weeks inbetween two challenges. When reproducibility during the same day was studied an average fall in FEV of 34% was found after the first inhalation and 34% decrease was found after the second challenge. When histamine challenge were done on two following days the fall in FEV was 25% on the first day and 28% on the second day. The average fall in FEV was 34% and 28% when reproducibility was studied with an interval of 12 weeks. No statistically significant difference was found between any of the compared challenges.

Histamine challenge in asthmatics at 07.00-12.00-17.00 and 22.00 h.

Nine adult asthmatics were challenged with histamine four times during the same day, at 07.00, 12.00, 17.00 and 22.00 h. A dose of histamine, which had induced a fall in FEV1 greater than 20%, when inhaled a few days before the study day, was used. The baseline values before the inhalations varied through the day. FEV1 was on average 1.9 liter at 07.00, 2.2 l. at 12.00, 2.2 l. at 17.00 and 2.0 l. at 22.00 h. The average decrease in per cent from the baseline after the inhalation of histamine was 27% at 07.00, 33% at 12.00, 29% at 17.00 and 28% at 22.00 h. A statistically significant difference in baseline FEV1 was measured during the day, but no statistically significant difference was found in the percentage decrease in FEV1 after inhalation of histamine, when measured at 07.00, 12.00, 17.00 and 22.00 h.

Regional V/Q changes in asthmatics after histamine inhalation.

The immediate changes in regional ventilation and pulmonary blood flow were studied in seventeen adults with perennial asthma and in two control persons, who were challenged by histamine inhalation (histamine induced asthma (HIA)). The studies were based on gammacamera images of 81mKr and of 99mTc labelled particles in the lungs and the results were compared with simultaneous changes in peak expiratory flow (PEF). No changes were observed in normal persons. After histamine inhalation the ventilation pattern became patchy, but no changes were seen in the blood flow distribution. PEF was markedly reduced. On repeated challenges ventilatory changes after HIA did not result in stereotypic images. HIA-defects were dissimilar to exercise- and antigen-induced defects when studied in the same patient(s) and were different, too, from the result in the same patients during a spontaneous asthmatic attack. The therapeutic and prophylactic effects of terbutaline were demonstrated in patients exposed to a histamine challenge.

Bronchial hyperreactivity in allergic subjects.

Bronchial hyperreactivity was studied in 79 patients who gave a history of allergic symptoms. Twenty-nine of them suffered from rhinitis, 28 from eczema, 21 from urticaria and one from gastrointestinal allergy. Forced expiration in the first second (FEV1) was measured in each. If FEV1 was greater than 1 l a histamine challenge was done. Histamine (0.6 mg/ml) was inhaled by tidal breathing for one minute. FEV1 was measured before the inhalation and two min after cessation of the inhalation. If FEV1 dropped greater than 20% the inhalation was assessed as positive and the provocation was stopped. If the challenge was not positive another inhalation with histamine (2.4 mg/ml, l min) was done. If FEV1 dropped greater than 20% when measured two min after the inhalation the provocation was called positive. Twenty-two patients with rhinitis had a negative bronchial challenge, six had a positive. One of them had asthma, three suffered also from cough and/or serous sputum production, and two had hay fever. Out of 28 with eczema, 20 had negative histamine challenge and five a positive. Four of these suffered from daily cough and/or serous sputum production, one had no airway symptoms. Fifteen out of 21 suffering from urticaria had a negative histamine challenge, three had a positive. Two of them suffered from asthma and one complained of daily cough and/or serous sputum production. It is concluded that allergic subjects without symptoms from the airways, have a bronchial reactivity to inhaled histamine similar to the general population.

Reproducibility of early asthmatic response to Cladosporium herbarum.

The reproducibility of the early asthmatic response after bronchial challenge with cladosporium herbarum was studied in 5 adult asthmatics. Four bronchial challenges were done in randomized order with an interval of one week. The four challenges were: cladosporium herbarum, cladosporium herbarum, histamine and saline. The bronchial challenges were done double-blind. Cladosporium herbarum was inhaled in the following concentrations (w/v): 1:100000, 1:10000, 1:1000 and up to 1:100. Histamine was inhaled in the following concentrations: 0.3, 0.6, 1.2 and up to 2.4 mg/ml FEV1 was measured before every inhalation and 2, 5, 10 min after. If FEV1 dropped greater than 20% after inhalation, the challenge was assessed as positive and the provocation on that day was stopped. The provocation was assessed as negative if this fall was not seen after the fourth inhalation. Two patients with positive skin test to cladosporium herbarum had reproducible early asthmatic response after inhalation of the antigen, they reacted to inhaled histamine and one of them presented an early asthmatic response after inhalation of saline. Three patients with negative skin test to cladosporium herbarum had an early asthmatic response after inhalation of the antigen on two out of six provocations, a response which was not reproducible. None of the three responded to saline. It is concluded that inhalation challenge with cladosporium herbarum may be more confusing than helpful in the diagnosis of early asthmatic response to this antigen, as patients with negative history and negative skin test sometimes present a positive bronchial challenge.

Reproducibility of the late asthmatic response.

The reproducibility of the late asthmatic response after bronchial challenge with cladosporium herbarum was studied in five adult asthmatics. Four bronchial challenges were done in randomized order with an interval of one week. The four challenges were: cladosporium herbarum, cladosporium herbarum, histamine and saline. The bronchial challenges were done double-blind. Up to four inhalations of the substance were given on one day. Cladosporium herbarum was inhaled in concentrations of 1:100000, 1:10000, 1:1000 and up to 1:100 w/v. Histamine was inhaled at concentrations of 0.3, 0.6, 1.2 and up to 2.4 mg/ml. The provocation was stopped if FEV1 dropped greater than 20% up to 10 min after the inhalation, or after the four inhalations. Ventilatory capacity was measured with one h intervals up to six h after the last inhalation. One patient with positive skin test to cladosporium herbarum had no late asthmatic reaction after inhaling a dose of antigen which gave an early asthmatic response. One patient with positive skin test and early asthmatic response after inhalation of cladosporium presented late asthmatic response after one provocation, but this response was not reproducible. None of the two patients with negative skin test had late asthmatic response after inhalation of the antigen, nor had they late asthmatic response after inhalation of saline or histamine. One patient with negative skin test and no early asthmatic response to inhaled cladosporium, showed reproducible late asthmatic response after antigen inhalation. This patient also presented late asthmatic response after saline inhalation, but not after histamine inhalation. It is concluded that late asthmatic response should be defined better than of fall from baseline greater than 20%.

Regional V/Q changes in asthmatics after antigen inhalation.

The immediate changes in regional ventilation and pulmonary blood flow were studied in five adults with perennial asthma, who were challenged with an allergen inhalation (pollen or moulds). The studies were based on gammacamera images of 81 mKr and of 99mTC labelled particles in the lungs and the results were compared with simultaneous changes in peak expiratory flow. Moderate to profound changes were observed after antigen-induced asthma (AIA), and ventilation and perfusion defects were matched in most regions. Peak expiratory flow was reduced in most of the cases after AIA.

Exercise-induced asthma after inhalation of aerosols with different osmolarities.

Five adult asthmatics completed five standardized exercise tests while inhaling aerosols with different osmolarities. The nebulized solutions were 2% NaCl (osmolarity = 616 mosm), 4% NaCl (osmolarity = 1232 mosm), 6.1% dextrose (osmolarity = 308 mosm = isoosmolar), 24.4% dextrose (osmolarity = 1232 mosm) and distilled water (osmolarity = 0). All the patients had EIA. During the study all conditions, except the osmolarity of the inhaled aerosols were kept constant. There was no statistical difference in the response to the exercise on the five days, the fall in PEF being 22.8% after exercise while inhaling 2% NaCl, 17.8% after inhaling 4% NaCl, 16.2 after inhaling 6.1% dextrose, 24.8% after inhaling 24.4% dextrose and 21.6% after exercise while inhaling nebulized distilled water, respectively. It is concluded that the osmolarity of the inhaled aerosol is of little or no importance in exercise-induced asthma.

Regional V/Q changes in asthmatics after exercise.

The immediate changes in regional ventilation and pulmonary blood flow were studied in fifteen adults with perennial asthma and in two control persons, who were challenged by moderate exercise on a treadmill or bicycle ergometer. Ventilation was studied before and immediately after the exercise, and again about five min after stopping the provocation. Peak expiratory flow was checked at regular intervals. Five min after cessation of the exercise ventilation had become patchy and irregular, but the pulmonary blood flow distribution remained "normal", i.e. as seen in the resting state. The ventilatory defects could be prevented by pretreatment with terbutaline or eliminated by terbutaline treatment after development of signs and symptoms. From repeat studies it can be concluded that the development of regional ventilatory defects after EIA do not follow a stereotypic course nor are defects similar to those provoked by histamine or allergens.

Lung function and bronchial hyperreactivity following exposure to four different temperatures and relative humidities.

Seven asthmatic patients were exposed to four different climatic conditions in a climate chamber. The four conditions were: 15 degrees C/30% relative humidity (RH), 15 degrees C/70% RH, 30 degrees C/30% RH and 30 degrees C/70% RH and the exposure time was 4 hours. Before and after the exposure the following lung function parameters were measured: PEF, FEV1, RV and TLC. After each exposure a bronchial challenge with histamine was performed by the doubling-dose principle. The results indicated no difference in lung function after exposure to the "extreme" conditions in this study (i.e. 15 degrees C/30% RH and 30 degrees C/70% RH, water content 3.5 and 19 g/kg dry air, respectively), while a decrease in RV and TLC was seen after exposure to the "middle" conditions (i.e. 15 degrees C/70% RH and 30 degrees C/30% RH, water content 7.5 and 8 g/kg dry air, respectively). No change in ventilatory capacity was seen, and the bronchial hyperactivity also remained unchanged. During the 4 hours exposure, measurements of FEV1 and PEF also remained constant. It is concluded that this kind of exposure is without great effect on the asthmatics condition.