Changes in specific airways conductance and forced expiratory volume in one second after a bronchodilator in normal subjects and patients with airways obstruction

Skinner, C. and Palmer, K.N.V. (1974).Thorax, 29, 574-577. Changes in specific airways conductance and forced expiratory volume in one second after a bronchodilator in normal subjects and patients with airways obstruction. Specific conductance (SGaw) and the forced expiratory volume in one second (FEV₁) were measured in 10 normal, 10 asthmatic, and 10 obstructive bronchitic subjects before and after aerosol salbutamol. Mean SGaw increased by 37% in normals, by 109% in asthmatics, and by 38% in obstructive bronchitics. Mean FEV₁ increased by 2% in normals, by 32% in asthmatics, and by 12% in obstructive bronchitics. SGaw appears to be a more sensitive indicator than FEV₁ of changes in airways calibre following a bronchodilator drug in normal subjects, but FEV₁ is as good an indicator of these changes as SGaw in patients with airways obstruction.     

Effects of airway calibre on lung delivery of nebulised salbutamol

BACKGROUND: A study was undertaken to test the hypothesis that airway calibre may alter lung deposition and therefore lung bioavailability of inhaled drugs as a result of narrowed airways reducing peripheral drug delivery. This was evaluated using the early lung absorption profile of salbutamol over the first 30 minutes after inhalation. METHODS: Three groups were compared: (1) 10 normal subjects with mean forced expiratory volume in one second (FEV1) 109.5% predicted and mid forced expiratory flow (FEF25-75) 103.0%, (2) 10 mild asthmatic patients with FEV1 102.0% and FEF25-75 82.6%, and (3) 10 severe asthmatic patients with FEV1 49.2% and FEF25-75 27.5% predicted. Each subject had one study visit where a single dose of nebulised salbutamol was given (40 micrograms/kg) via a Ventstream nebuliser with mouthpiece followed by mouth rinsing. Plasma salbutamol levels were measured at five, 10, 20, and 30 minutes after the end of nebulisation with calculation of maximal (Cmax) and average (Cav) concentration over 0-30 minutes. Systemic beta 2 responses (plasma potassium, tremor and heart rate) and airway responses (FEV1, FEF25-75) were measured before and 30 minutes after nebulisation. RESULTS: For Cav over 0-30 minutes the severe asthmatic patients had a lower plasma salbutamol concentration (1.31 ng/ml) than either the normal subjects (2.40 ng/ml) or those with mild asthma (2.45 ng/ml): normal subjects versus severe asthmatics 95% CI 0.30 to 1.88, mild versus severe asthmatics 95% CI 0.07 to 2.21. Airway responses as delta FEF25-75 were lower in the severe asthmatic subjects (0.30 l/s) than in either the normal subjects (0.69 l/s) or those with mild asthma (0.74 l/s): normal subjects versus severe asthmatic subjects 95% CI 0.09 to 0.88, mild versus severe asthmatics 95% CI 0.04 to 0.93. Values for delta log tremor also showed attenuated responses in those with severe asthma (1.22 mg2/s) compared with normal subjects (2.00 mg2/s) or those with mild asthma (2.02 mg2/s): normal subjects versus those with severe asthma 95% CI -0.02 to 3.30, mild versus severe asthmatics 95% CI 0.02 to 3.30. CONCLUSIONS: These results show that baseline airway calibre significantly alters the early lung absorption profile of salbutamol in patients with severe asthma. This may have implications in terms of optimising dose and delivery of inhaled beta 2 agonists in these patients.


     

Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma.

The effect of 5 mg nebulised salbutamol on the cardiorespiratory responses to a progressive maximal exercise test was investigated in eight asthmatic (mean forced expiratory volume in one second (FEV1) 3.48 (1.0) litres) and eight non-asthmatic men. Exercise tests were performed on a bicycle ergometer after administration of nebulised salbutamol or matched saline placebo. In the asthmatic subjects salbutamol increased the resting FEV1 by 11%. The mean (SD) percentage fall in FEV1 after exercise did not change significantly (salbutamol 9.4 (12.8); placebo 15.0 (8.0], but because the FEV1 before exercise was increased the lowest FEV1 after exercise was also significantly higher after salbutamol than placebo (3.60 (1.13) v 2.85 (0.80) litres). Despite the improvement in FEV1 before exercise there was no significant difference in maximal workload, oxygen uptake, heart rate, or ventilation during exercise after salbutamol compared with placebo in the asthmatic patients. Tidal volume was higher at maximal exercise after salbutamol but there was no change in perception of breathlessness or exertion in the asthmatic subjects. During submaximal progressive exercise the perceived rate of exertion was reduced in the asthmatic patients and oxygen pulse was reduced in both groups owing to a small and non-significant increase in heart rate. The FEV1 and cardiorespiratory response to the progressive maximal exercise test in the non-asthmatic subjects were otherwise unchanged after salbutamol. The results suggest that 5 mg nebulised salbutamol has little effect on the cardiorespiratory responses to progressive maximal exercise in patients with mild asthma and in non-asthmatic subjects. Salbutamol in this dose may reduce the severity of exercise induced asthma, but no ergogenic effect on maximal exercise performance was shown.     

Prostaglandins and the control of airways responses to histamine in normal and asthmatic subjects.

Inhalation histamine challenges were performed in groups of normal and asthmatic subjects. On each occasion a regression line for the descending part of the log-cumulative dose-response curve was computed. The dose of histamine causing a 20% fall in specific conductance (sGaw) was taken as an index of "sensitivity." The slope gave the "reactivity". In a double-blind, randomised study the potent inhibitor of prostaglandin synthesis indomethacin (50 mg four times per day for three days) was associated with a small but significant bronchodilatation in the normal but not the asthmatic subjects. Sensitivity to histamine was considerably decreased in the asthmatic patients (p less than 0.005) but unchanged in the normal subjects. In both groups reactivity was significantly increased (p less than 0.01). The study was repeated after several weeks of regular salbutamol treatment. In both groups salbutamol caused a decrease in sensitivity (p less than 0.001) but no change in reactivity. After indomethacin had been reintroduced while salbutamol was continued most of the effects of chronic salbutamol treatment were reversed in the normal subjects, with a similar trend in the asthmatic patients. In both groups the dose-response curves after indomethacin treatment were little affected by pretreatment with salbutamol. Beta-adrenergic stimulation induces changes in the airways that may be dependent on prostaglandin production.     

Interactions between response to inhaled prostaglandin E2 and chronic beta-adrenergic agonist treatment.

Cumulative inhalation dose-response curves for the response to prostaglandin E2 (PGE2) have been constructed in normal subjects and patients with mild, stable asthma. In normal subjects cumulative inhalation dose-response curves were also constructed for salbutamol. In normal subjects dose-related bronchodilatation occurred in response to both PGE2 and salbutamol, although both the within-subject and the between-subject variation was significantly greater with salbutamol. Most asthmatic subjects gave a biphasic response to PGE2 on at least one occasion, PGE2 being a bronchoconstrictor above a certain level of specific airways conductance (sGaw) and a bronchodilator below. Chronic treatment with inhaled salbutamol (400 micrograms four times a day) had no effect on the normal subjects' response to salbutamol but there was a significant shift of the PGE2 dose-response curve to the left, indicating increased bronchodilatation (p less than 0.02). Stabilisation of the asthmatics' dose-response curve in the direction of bronchodilatation also occurred and was more pronounced (p less than 0.005). In the normal subjects PGE2 may be concerned in the control of airway smooth-muscle tone and in limiting bronchoconstriction induced by mediators such as histamine, and chronic salbutamol treatment may be important in enhancing these effects of PGE2. 80 mg oral propranolol given one and a half hours before had no effect on PGE2-induced bronchodilatation; but the question whether chronic treatment with beta-blockers has any effect needs investigation.     

Tracheobronchial mucociliary clearance in asthma: impairment during remission.

Tracheobronchial mucociliary clearance was measured in eight non-smoking patients with asthma in complete remission. The patients were symptom free and required no medication whatsoever for one to six months before assessment. Mucociliary clearance was measured with an objective, radioaerosol technique. For comparison, mucociliary clearance of eight non-smoking, healthy subjects with physical characteristics and pulmonary function similar to those of the asthmatics was also measured on two occasions. In their first assessment the healthy subjects inhaled the tracer radioaerosol under experimental conditions similar to those used for the asthmatics; in the second assessment they inhaled the radioaerosol rapidly to simulate the asthmatic pattern of deposition. Under similar experimental conditions the radioaerosol was deposited more proximally in the asthmatic subjects than in the normal subjects and the difference was statistically significant (p less than 0.01). When, however, the depth of radioaerosol lung penetration was similar in the two groups, there was evidence of a significantly (p less than 0.01) poorer mucociliary clearance six hours after radioaerosol inhalation in the asthmatic than in the healthy group. These findings raise the question whether asthma ever remits completely.     

Beta-blockers in bronchial asthma: effect of propranolol and pindolol on large and small airways.

In 11 asthmatic subjects the relative magnitude and the site of airway bronchoconstriction were compared after the oral administration of 40 mg of propranolol and 2.5 mg of pindolol and the magnitude and site of bronchodilation produced by 0.5 mg subcutaneous terbutaline were tested after pretreatment with propranolol and pindolol. Specific airway conductance (sGaw) and peak expiratory flow rate (PEFR), both believed to reflect changes in large airways, and capacity isoflow (Ciso-v) and delta Vmax50, both believed to reflect changes in small airways, were determined before and after administration of placebo, pindolol, and propranolol. Treatments were given double blind and in random order. After the administration of propranolol we noted a significant bronchoconstrictive effect in the large airways (mean values of PEFR and sGaw, expressed as percentages of control values, decreased by 87.4% +/- 13.2% and 43.3% +/- 8.9%) and in the small airways (mean value of Ciso-v increased by 20.6% +/- 4.7% and that of delta Vmax50 decreased by 50% +/- 11.9% of control). By contrast, pindolol produced no significant effect on sGaw or PEFR but the tests of small airway function showed significant bronchoconstriction (mean values of Ciso-v increased by 12.9% +/- 2.6% and those of delta Vmax50 decreased by 47.2% +/- 9.2%). This action makes pindolol potentially dangerous in asthmatic patients. The bronchodilator action of terbutaline on large airways is diminished after the use of both propranolol and pindolol.     

Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma

BACKGROUND: Respiratory infections are well known triggers of asthma exacerbations, but their role in stable adult asthma remains unclear. METHODS: 103 asthmatics and 30 control subjects were enrolled in the study. Sputum was induced by inhalation of 3% NaCl solution. Oropharyngeal swab specimens were obtained from the posterior wall of the oropharynx. Respiratory specimens were analysed by RT-PCR for rhinovirus, enterovirus and respiratory syncytial virus and by PCR for adenovirus, Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis. RESULTS: Sputum samples from two of the 30 healthy controls (6.7%), five of 53 patients with mild asthma (9.4%), and eight of 50 with moderate asthma (16.0%) were positive for rhinovirus. Rhinovirus positive asthmatic subjects had more asthma symptoms and lower forced expiratory volume in 1 second (FEV(1)) (79% predicted) than rhinovirus negative cases (93.5% predicted; p = 0.020). Chlamydia pneumoniae PCR was positive in 11 healthy controls (36.6%), 11 mild asthmatics (20.8%), and 11 moderate asthmatics (22%), and PCR positive asthmatics had lower FEV(1)/FVC than negative cases (78.2% v 80.8%, p = 0.023). Bordetella pertussis PCR was positive in 30 cases: five healthy controls (16.7%), 15 mild asthmatics (28.3%), and 10 moderate asthmatics (20%). Bordetella pertussis positive individuals had lower FEV(1)/FVC (77.1% v 80.7%, p = 0.012) and more asthma symptoms than B pertussis negative cases. CONCLUSIONS: Rhinovirus, C pneumoniae, and B pertussis are found in the sputum or pharyngeal swab specimens of asthmatic subjects without concurrent symptoms of infection or asthma exacerbation, as well as in some healthy controls. Positivity is associated with lower lung function and more frequent asthma symptoms.     

Both local anesthetics and salbutamol pretreatment affect reflex bronchoconstriction in volunteers with asthma undergoing awake fiberoptic intubation

BACKGROUND: Awake tracheal intubation may evoke reflex bronchoconstriction in asthmatics. Whether this effect is altered by the choice of the local anesthetic used or by pretreatment with a beta2-adrenoceptor agonist is unknown. Therefore, we assessed the effect of awake fiberoptic intubation after lidocaine or dyclonine inhalation with or without pretreatment with salbutamol on lung function in asthmatic volunteers. METHODS: Bronchial hyperreactivity was verified by an inhalational histamine challenge. On four different days in a randomized, double blind fashion the volunteers (n = 10) inhaled either dyclonine or lidocaine with or without salbutamol pretreatment. FEV1 was measured at baseline, following salbutamol or saline inhalation, after lidocaine or dyclonine inhalation, while intubated, and after extubation. Lidocaine and dyclonine plasma concentrations were also measured. Statistics: Two-way ANOVA, post hoc tests with Bonferroni correction, results are presented as mean +/- SD. RESULTS: Neither lidocaine nor dyclonine inhalation changed FEV1 significantly from baseline compared with placebo inhalation (4.43 +/- 0.67 l vs. 4.29 +/- 0.72 l, and 4.53 +/- 0.63 l vs. 4.24 +/- 0.80 l, respectively). Salbutamol slightly but significantly increased FEV1 (4.45 +/- 0.76 l vs. 4.71 +/- 0.61 l, P = 0.0034, and 4.48 +/- 0.62 l vs. 4.71 +/- 0.61 l, P = 0.0121, respectively). Following awake intubation FEV1 significantly decreased under lidocaine topical anesthesia (4.29 +/- 0.72 l to 2.86 +/- 0.87 l) but decreased even more under dyclonine anesthesia (4.24 +/- 0.80 l to 2.20 +/- 0.67 l; P < 0.0001). While salbutamol pretreatment significantly attenuated the response to intubation, it did not eliminate the difference between the effects of lidocaine and dyclonine. Only minutes after extubation FEV1 was similar compared with baseline. CONCLUSION: In asthmatics, awake fiberoptic intubation evokes a more than 50% decrease in FEV1 following dyclonine inhalation. Using lidocaine for topical anesthesia the decrease in FEV1 is significantly mitigated (35%) and can be even further attenuated by salbutamol pretreatment. Therefore, combined treatment with lidocaine and salbutamol can be recommended for awake intubation while the use of dyclonine, despite its excellent and longer lasting topical anesthesia, may be contraindicated in patients with bronchial hyperreactivity.     

Mechanisms of sulphur dioxide induced bronchoconstriction in normal and asthmatic man.

We have examined the inhibitory effect of atropine and sodium cromoglycate (SCG) on the bronchial response to sulphur dioxide (SO2) in groups of normal and asthmatic subjects. Eleven normal subjects were premedicated with propranolol (100 mg orally) one hour before each experiment. After baseline measurements of specific airways conductance (sGaw) the subject inhaled an aerosol from a Wright nebuliser for five minutes. In separate experiments this contained water (control), atropine methonitrate (0 . 2%), or SCG (1%). Fifteen minutes later sGaw was remeasured and the subject then breathed SO2 (8 ppm) for three minutes through the mouth. Specific airways conductance was measured for the duration of the subsequent response. Intervals between experiments on any one subject were one week or more. After control SO2 inhalation sGaw decreased in all subjects (mean 34 +/- 17 (SD)%). Atropine and SCG significantly inhibited the SO2 response (p less than 0 . 01 for both). After atropine the mean decrease in sGaw was 13 +/- 24%; after SCG 16 +/- 12% (range -3- + 55%). With atropine the degree of inhibition was inversely related to the subject's responsiveness to the control SO2 inhalation (r = 0 . 75; p less than 0 . 01). In four asthmatics (without beta-blockade and with lower SO2 exposure) atropine did not inhibit the SO2 response; SCG had a similar effect to that seen in normal subjects. Therefore, vagal efferent mechanisms are involved in the bronchial response to SO2 in normal subjects, but the lack of inhibition caused by atropine in hyperreactive normal and asthmatic subjects suggests that vagal mechanisms are not important in the causation of hyperreactivity to SO2. The mechanism of inhibition with SCG is unknown.     

Influence of age on response to ipratropium and salbutamol in asthma.

We studied the differential response to inhaled salbutamol and ipratropium of 29 asthmatic patients, 18 intrinsic, 11 extrinsic, using peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Thirty minutes after a theoretically maximally bronchodilating dose of salbutamol (400 microgram) or ipratropium (80 microgram), second doses frequently caused further bronchodilatation. We suspect that second doses may reach bronchi untouched by the first inhalation. Analysis of variance showed a powerful intrinsic versus extrinsic effect, and there were clearly differences between patients in their response to treatment (patient versus drug interaction) but these differences were not removed by dividing the patients into intrinsic and extrinsic groups. Results for the group as a whole favoured salbutamol, but examination of individual results by a pattern-recognition technique showed ipratropium equally effective in eight patients and more effective in three. All patients with a definite predominant salbutamol response were less than 40 years old. The response to salbutamol declined significantly with age, whereas that to ipratropium did not. In general in patients aged less than 40 years salbutamol is the drug of choice. With advancing age, and the apparent decline of beta-adrenergic responsiveness, the initially comparatively small response to ipratropium becomes relatively more important and may predominate. In older patients ipratropium, or continued therapy with both drugs, may be preferable.     

Airway response to salbutamol: effect of regular salbutamol inhalations in normal, atopic, and asthmatic subjects.

This study was designed to determine whether resistance to the airway effects of the beta-agonist, salbutamol, would develop in three groups of subjects while taking large doses of inhaled salbutamol. Six normal non-atopic, six atopic non-asthmatic, and eight atopic asthmatic subjects were studied by an identical technique. The development of resistance was assessed from salbutamol dose-response studies in which the airway response was measured as specific airway conductance (sGaw). Further evidence was sought in the atopic and asthmatic subjects by measuring the airway response to a standard histamine inhalation challenge and the protective effect of 100 micrograms salbutamol on this challenge, and by six-hourly peak flow recordings. Subjects were assessed before and during four weeks in which they took inhaled salbutamol regularly in doses increasing to 500 microgram quid in week 4. Normal subjects showed a progressive reduction in the bronchodilator (sGaw) response to salbutamol during the four weeks, indicating the progressive development of resistance. The atopic subjects, both asthmatic and non-asthmatic, showed no reduction in the response to salbutamol during the four weeks, nor any change in the response to histamine challenge or in regular peak flow readings. These results demonstrate that asthmatic patients do not develop bronchial beta-adrenoceptor resistance easily and suggests that they and atopic non-asthmatic subjects are less susceptible to its development than normal subjects.     

A COMPARISON OF THE EFFECT ON AIRWAY RESISTANCE OF A NEW BETA BLOCKING DRUG, ICI.50,172 AND PROPRANOLOL

A new beta-adrenergic receptor blocking agent, ICI.50,172, hasbeen compared with propranolol with respect to the effects onairway resistance (AWR), forced expiratory volume (FEV₁) andpulse rate. AWR was measured by body plethysmography. The drugswere given intravenously to ten asthmatic patients on differentoccasions. ICI.50,172 caused no subjective alteration of theirrespiratory condition, and only a slight increase in AWR. Propranololcaused dyspnoea and wheeze in all but one of the subjects togetherwith a marked increase in AWR. It is concluded that ICI.50,172can safely be administered to asthmatic patients and that itsintroduction could represent an important advance in beta blockingtherapy.     

Bone ultrasonometric features and growth hormone secretion in asthmatic patients during chronic inhaled corticosteroid therapy

BACKGROUND: Quantitative ultrasound bone densitometry (QUBD) is a new method to assess bone mineral density and bone microarchitecture. Corticosteroid (CS) therapy may diminish bone mass, alter bone quality and may influence growth hormone (GH) secretion and bone metabolism markers. Therefore, the aim of this study was to evaluate the effects of long-term therapy with inhaled CSs (ICSs) on structural bone characteristics and their correlations with GH secretion and bone markers in asthmatic patients. METHODS: In a cross-sectional study, we enrolled 60 adult patients with mild to moderate persistent asthma: 22 on chronic (>1 year) ICS therapy, 10 naive to ICSs treatment and 28 healthy control subjects. The groups were matched for age and BMI. Each subject underwent to QUBD at the phalanxes to assess bone microarchitecture by ultrasound bone profile index (UBPI), bone density by amplitude-dependent speed of sound (AdSos); test with GH-releasing hormone (GHRH) injection with calculation of peak GH and the Delta GH (peak GH-basal GH); and hormonal and bone markers measurements. RESULTS: Asthmatics treated with long-term ICS therapy showed a lower UBPI (P < 0.01) compared to controls (49.8 +/- 19.3 vs. 77.0 +/- 10.1, respectively) and to asthmatics never taking ICSs (73.2 +/- 9.6). In ICS-treated asthmatics, DeltaGH and GH-peak showed a significant correlation with UBPI. A significant difference was observed comparing asthmatics treated with ICSs to controls and asthmatics naive to ICSs in GH response to GHRH iv bolus. Serum osteocalcin was significantly reduced in asthmatic patients treated with ICSs. CONCLUSIONS: In asthmatic patients, long-term ICSs treatment produces negative effects on bone quality assessed by QUBD, and such effects are associated to an impaired GH secretion.     

Metabolic intervention in surgical patients: the effect of alpha- or beta-blockade on glucose and protein metabolism in surgical patients receiving total parenteral nutrition

We performed a series of isotopic studies on the role of alpha- or beta-adrenergic activity in the regulation of glucose and protein metabolism in a group of surgical patients receiving total parenteral nutrition. We quantitated rates of glucose turnover and net protein breakdown by the primed constant infusion of 3H-glucose and 14C-urea, respectively. Basal measurements were first performed, and then the effect of either alpha- or beta-adrenergic blockade was assessed by means of the constant infusion of either phentolamine or propranolol. In addition, we assessed the effect of beta-stimulation by infusing the beta-agonist, salbutamol. The institution of alpha-adrenergic blockade did not significantly alter either the plasma glucose level or the rate of glucose production. However, the rate of net protein catabolism decreased significantly after alpha-adrenergic blockade. Before alpha-blockade the value for NPC was 0.88 +/- 0.27 gm/kg/day, and after alpha-blockade the corresponding value was 0.73 +/- 0.24 gm/kg/day (p less than 0.01). beta-Adrenergic blockade resulted in a decrease in the rate of glucose appearance from 38.2 +/- 6.1 mumol/kg/min to 35.1 +/- 5.7 mumol/kg/min, and the plasma glucose clearance increased from 5.0 +/- 0.8 ml/kg/min to 5.4 +/- 0.8 ml/kg/min. As a result of these changes the plasma glucose concentration decreased significantly (p less than 0.01) from 7.4 +/- 0.3 mumol/ml to 6.5 +/- 0.5 mumol/ml. beta-Adrenergic blockade did not significantly decrease the rate of net protein catabolism. beta-Stimulation with salbutamol resulted in a significant increase (p less than 0.05) in the rate of glucose production from 31.3 +/- 4.2 mumol/kg/min to 38.0 +/- 6.5 mumol/kg/min, and as a result the plasma glucose level increased significantly from 6.7 +/- 0.6 mumol/ml to 7.4 +/- 0.6 mumol/ml (p less than 0.04). We conclude from these studies that the role of the adrenergic nervous system in the promotion of endogenous glucose turnover in surgical patients receiving total parenteral nutrition is primarily a beta-adrenergic effect, whereas the promotion of protein catabolism is mainly an alpha-adrenergic effect.     

Differences in radiological/HRCT findings in eosinophilic bronchitis and asthma: implication for bronchial responsiveness

BACKGROUND: Airway hyperresponsiveness in asthmatics is considered to be one of the major consequences of airway inflammation and remodelling. Airway responsiveness is normal in patients with eosinophilic bronchitis (EB), despite eosinophilic inflammation of the airways comparable to that which occurs in asthmatics. Comparisons between asthma and EB should clarify the changes in airway morphology that are related specifically to AHR in asthmatics. METHODS: Eighteen asthmatic patients, 15 patients with EB, and 11 healthy subjects were recruited. Airway wall area percentage (WA%), centrilobular prominence, and air trapping were compared using thin slice section computed tomography. RESULTS: WA% was significantly greater in asthmatics than in patients with EB (72 (3.1)% v 54 (2.1)%, p = 0.032) and was similar in EB patients and controls (54 (2.1)% v 57 (1.8)%, p>0.05). Centrilobular prominence and air trapping were similar in EB patients and asthmatics and were significantly greater than in controls. CONCLUSION: WA% rather than air trapping or centrilobular prominence may be associated with the airway hyperresponsiveness that occurs in asthmatics but not in patients with EB.     

Effects of propranolol on human postoperative ileus

BACKGROUND: The sympathetic nervous hyperactivity present in response to surgical stress has been implicated as an important component of the postoperative paralytic ileus. A randomized and prospective study was conducted, evaluating the effects of the preoperative beta-adrenergic blockade with propranolol in schistosomotic patients during the period of postoperative ileus. METHODS: The study compared schistosomotic patients submitted, or not, to beta-adrenergic blockade. Basal cardiac frequency was determined and propranolol was used in a dose of 40 mg twice a day. The dose was adjusted weekly until a minimum decrease of 20% in cardiac frequency was achieved. Three coupled bipolar electrodes were placed in the left colon in both groups, and registration of myoelectric activity of the left colon was made twice a day during the period of postoperative ileus using a system of data collection (DATA Q Series 200). The electric signals were previously amplified, filtered and separated into Electric Control Activity (ECA) and Electric Response Activity (ERA). RESULTS: The dose of propranolol varied from 80 to 160 mg/day. The proportional decrease in basal heart frequency varied from 20 to 33%, with an average of 25.4 +/- 3.9% in the propranolol group, maintaining a mean of 24.3 +/- 3.6% decrease in the postoperative period. Differences on clinical recovery of the postoperative ileus were not found. Significant differences on electromyographic patterns were not observed between the groups, except for the presence of a greater number of short-duration contractions in the second postoperative day in the beta-blocked group. CONCLUSION: The authors suggest that the preoperative beta-adrenergic blockade with propranolol does not determine myoelectric activity changes that could contribute to an earlier resolution of postoperative ileus.     

Effect of nifedipine on bronchoconstriction induced by inhalation of cold air

The effect of nifedipine (20 mg sublingually) on the bronchial response to cold air was studied in eight asthmatic patients and eight normal subjects. Eucapnic hyperventilation with dry subfreezing air was performed for three minutes by each subject, with a minute volume of 30 X FEV1 for normal subjects and half that for the asthmatics. In the normal subjects there was no difference in the falls in the one-second forced expiratory volume (FEV1) and specific airways conductance (sGaw) produced by cold air inhalation on the days when they were pretreated with placebo and with nifedipine. In asthmatic patients, however, significant protection with nifedipine was demonstrated. The maximum recorded fall in FEV1 was reduced from 13% +/- 2% (SE) to 4% +/- 2% (p less than 0.005) and the maximum fall in sGaw from 35% +/- 5% to 17% +/- 4% (p less than 0.002). The possible causes of this difference are discussed. It is suggested that these results present further evidence for a different mechanism of response to cold air in asthmatic and normal subjects.     

Both Local Anesthetics and Salbutamol Pretreatment Affect Reflex Bronchoconstriction in Volunteers with Asthma undergoing Awake Fiberoptic Intubation

Background: Awake tracheal intubation may evoke reflex bronchoconstriction in asthmatics. Whether this effect is altered by the choice of the local anesthetic used or by pretreatment with a [beta]2-adrenoceptor agonist is unknown. Therefore, we assessed the effect of awake fiberoptic intubation after lidocaine or dyclonine inhalation with or without pretreatment with salbutamol on lung function in asthmatic volunteers.

Methods: Bronchial hyperreactivity was verified by an inhalational histamine challenge. On four different days in a randomized, double blind fashion the volunteers (n = 10) inhaled either dyclonine or lidocaine with or without salbutamol pretreatment. FEV1 was measured at baseline, following salbutamol or saline inhalation, after lidocaine or dyclonine inhalation, while intubated, and after extubation. Lidocaine and dyclonine plasma concentrations were also measured. Statistics: Two-way ANOVA, post hoc tests with Bonferroni correction, results are presented as mean +/- SD.

Results: Neither lidocaine nor dyclonine inhalation changed FEV1 significantly from baseline compared with placebo in-halation (4.43 +/- 0.67 l vs. 4.29 +/- 0.72 l, and 4.53 +/- 0.63 l vs. 4.24 +/- 0.80 l, respectively). Salbutamol slightly but significantly increased FEV1 (4.45 +/- 0.76 l vs. 4.71 +/- 0.61 l, P = 0.0034, and 4.48 +/- 0.62 l vs. 4.71 +/- 0.61 l, P = 0.0121, respectively). Following awake intubation FEV1 significantly decreased under lidocaine topical anesthesia (4.29 +/- 0.72 l to 2.86 +/- 0.87 l) but decreased even more under dyclonine anesthesia (4.24 +/- 0.80 l to 2.20 +/- 0.67 l;P < 0.0001). While salbutamol pretreatment significantly attenuated the response to intubation, it did not eliminate the difference between the effects of lidocaine and dyclonine. Only minutes after extubation FEV1 was similar compared with baseline.     

A comparative study of atropine methonitrate, salbutamol, and their combination in airways obstruction.

Dose-response relationships of the cholinergic antagonist, atropine methonitrate, and the beta-adrenergic agonist, salbutamol, were examined by cumulative dose techniques. A wet aerosol, 1.5 mg atropine methonitrate produced a maximum response. The response to 200 microgram of salbutamol from a pressurised aerosol was close to maximum. Secondly, the bronchodilator response of salbutamol microgram was compared with atropine methonitrate 2 mg and placebo in 18 asthmatic patients in a randomised crossover study. In 11 of them the bronchodilator response of the combination of salbutamol and atropine methonitrate was evaluated. Atropine methonitrate produced a similar peak bronchodilator effect to salbutamol, but its effect was more prolonged, the response being significantly greater at four and six hours than with salbutamol. The combination of drugs produced a significantly greater and more lasting bronchodilatation than either of the drugs alone. Despite mild side effects, atropine methonitrate, either alone or in combination with an adrenergic drug, appears to have a place in the treatment of sever reversible airway obstruction not adequately controlled by conventional treatment.