Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis.

Fatigue in the immune mediated inflammatory disease sarcoidosis is thought to be associated with impaired exercise tolerance. This prospective study assessed fatigue and recuperative capacity after repeated exercise, and examined whether changing concentrations in biomarkers upon exercise are associated with fatigue. Twenty sarcoidosis patients and 10 healthy volunteers performed maximal cardiopulmonary exercise tests on two successive days. Concentrations of cytokines, stress hormones, ACE and CK were assessed before and after the two exercise tests, and 3 days thereafter. All participants completed a sleep diary. Severely fatigued patients showed significant lower VO2 max (p=0.038, p=0.022) and maximal workload (p=0.034, p=0.028) on both exercise tests compared to healthy controls. No impairment of maximal exercise testing was demonstrated during the second cycling test in any group. Fatigue was not correlated with changes in concentrations of biomarkers upon exercise. Severely fatigued patients rated both tests as significantly more fatiguing, and reported significant lower mean subjective night sleeping time during the testing period. Fatigue in sarcoidosis patients cannot be objectified by reduction of exercise capacity after repeated maximal exercise testing, and is not correlated with significant changes in biomarkers. Severe fatigue is only and consistently featured by patient reported outcomes.

Metabolic acidosis improves airway conductance in patients with asthma.

The objective was to investigate whether acute metabolic acidosis could cause bronchodilation in patients with asthma. Twelve patients with asthma (8 females, mean age 39 (+/- SD 12) years, forced expiratory volume in 1 second [FEV(1)] 93 [+/-9] % predicted, PC(20) 1.9 (+/-1.0) mg/mL) participated in a double-blind, placebo-controlled trial. Subjects ingested calculated amounts of ammonium chloride to induce acidosis or saline as placebo, in random order, each on a separate day. Airway resistance (R(aw)), specific airway conductance (sG(aw)), FEV(1), and PEF were measured as primary variables. To evaluate the consequences of alterations in bronchial contractility on the airway responsiveness, the histamine provocation test (PC(20)) was measured as secondary variable. The intervention resulted in a mean (SD) decrease in base excess from -0.5 (+/-1.4) to -3.9 (+/-1.1) mmol/L (p < 0.01) and a decrease in pH from 7.41 (+/-0.02) to 7.36 (+/-0.02) (p < 0.01). This caused a statistically significant increase in sG(aw) from 1.15 (+/-0.16) to 1.26 (+/-0.13) 1/kPa.s) (p < 0.05). Tendencies towards increase were found in PEF (7.79 (+/-2.2) versus 8.09 (+/-1.9) (NS, p = 0.10) and in FEV(1) (2.98 (+/-0.9) versus 3.06 (+/-0.9) (NS, p = 0.15). PC(20) did not change significantly. It was concluded that acute metabolic acidosis has a modest bronchodilating effect in patients with asthma.

[Dyspnoea caused by upper-airway obstruction: simple diagnosis by establishing a flow-volume loop]. / Dyspneu door vernauwing in de bovenste luchtwegen: eenvoudige diagnostiek met een flowvolumecurve.

Three patients, men aged 72, 78 and 19 years, experienced shortness of breath and laboured breathing. All three had an upper-airway obstruction detected by a flow-volume loop and confirmed by bronchoscopy. The first patient had oesophageal carcinoma with vocal-cord paralysis and soon died. The second patient had a large struma; flow-volume loop improved after strumectomy. The third patient was diagnosed with extragonadal testicular carcinoma. The flow-volume loop improved after the first chemotherapy session. Flow-volume loop is an easy, non-invasive diagnostic tool that can be used even in severely-ill patients. It can provide information about the location of the obstruction and can differentiate between obstructive pulmonary disease and upper-airway obstruction. Therefore, it is recommended to obtain a flow-volume loop during the assessment of patients with upper airway obstruction.

Tension pneumopericardium caused by positive pressure ventilation complicating anaerobic pneumonia.

A 22-year-old man was admitted with pneumonia. He was immediately intubated and positive pressure ventilation was initiated. Blood and sputum cultures showed Bacteroides fragilis and Corynebacterium sp., which were treated with metronidazole and clindamycin. Three weeks later his blood pressure suddenly dropped with an elevation of the central venous pressure. Chest X-ray revealed a pneumopericardium. A parasternal mediastinotomy with partial pericardiectomy was immediately performed. On opening the pericardium his blood pressure normalised. The patient gradually recovered and six weeks after admission he was extubated. Two weeks later he was discharged. A pneumopericardium without previous thorax trauma is very rare and early recognition is imperative because a tension pneumopericardium with cardiac tamponade may develop, as happened in this case. A tension pneumopericardium has to be treated with immediate pericardiocentesis followed by partial pericardiectomy to avoid recurrence.

Inhaled corticosteroids, combined with long-acting beta(2)-agonists, improve the perception of bronchoconstriction in asthma.

The relationship between asthma medication and the perception of asthma symptoms is of interest for daily practice. Poor perception of asthma symptoms might influence patients' health care behavior and subsequently might lead to undertreatment and deterioration of their disease. This study investigated the influence of the chronic use of short-acting and long-acting beta(2)-agonists, compared with the additional use of inhaled corticosteroids on the perception of histamine-induced bronchoconstriction. Patients with asthma (33 male and 31 female, mean age 35 +/- 11 yr, FEV(1) 87 +/- 14% of the reference value, PC(20) geometric mean 1.08 mg/ml (95% CI: 0.76-1.52) were selected and randomly allocated to the use of either a short-acting beta(2)-agonists (salbutamol, n = 22) or a long-acting beta(2)-agonists (formoterol, n = 22) or placebo (n = 20), which has been used for 12 wk. This medication treatment was repeated exactly 1 yr later, with patients receiving the same medication plus an inhaled corticosteroid. Perception of histamine-induced bronchoconstriction was measured at the start of each treatment period and every 4 wk thereafter. Subjects quantified their sensation of respiratory discomfort during the challenge tests on a modified Borg scale. The perceptive "sensitivity" for changes in FEV(1) was analyzed by the linear regression slope (alpha) "Borg versus percentage fall in FEV(1)." The "absolute perceptual magnitude" was determined by the perception score at the 20% fall in FEV(1) (PS(20)). The additional use of inhaled corticosteroids during the second year resulted in an improved perception of histamine-induced bronchoconstriction (slope alpha) compared with the first year for only the long-acting beta(2)-agonists group (p value 0.036). This improvement was not observed for the "absolute perceptual magnitude" (PS(20)). The additional use of inhaled corticosteroids during chronic use of long-acting beta(2)-agonists improves the perceptive "sensitivity" for changes in FEV(1) during histamine-induced bronchoconstriction, which was not observed for short-acting bronchodilators. This result might indicate that the positive effects on perception of airway obstruction might be another reason (besides the beneficial effects on the clinical condition) for prescribing a combination of long-acting beta(2)-agonists and inhaled steroids.

Underestimation of nocturnal hypoxemia due to monitoring conditions in patients with COPD.

STUDY OBJECTIVES: COPD patients run a risk of developing nocturnal oxygen desaturation. When evaluating patients with nocturnal hypoxemia, an unfamiliar hospital environment and the monitoring equipment may cause sleep disturbances. It was hypothesized that increased sleep disruption will lead to fewer instances of desaturation during a night of monitoring. DESIGN: The following forms of monitoring were evaluated prospectively on 3 nights for each patient: oximetry at home; polysomnography (PSG) at home; and PSG in the hospital. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem, The Netherlands. PATIENTS: Fourteen stable COPD patients (7 men; median age, 71.5 years; age range, 59 to 81 years; FEV(1), 32.5% predicted; FEV(1) range, 19 to 70% predicted) participated in the study. All subjects had significant instances of nocturnal arterial oxygen desaturation. Those patients with a sleep-related breathing disorder or cardiac failure were excluded from the study. MEASUREMENTS AND RESULTS: The mean nocturnal arterial oxygen saturation (SaO(2)) level was higher during PSG monitoring at home (89.7%; range, 77 to 93%) than during oximetry monitoring (88.5%; range, 80 to 92%) [p < 0.025]. The fraction of time spent in hypoxemia (ie, SaO(2) < 90%) was lower during PSG monitoring at home (40.8%; range, 5 to 100%) than during oximetry monitoring (59.9%; range, 6 to 100%) [p < 0.01]. Desaturation time (DeltaSaO(2) > 4%) was lower during PSG monitoring at home (22.1%; range, 3 to 63%) during PSG monitoring at home than during oximetry monitoring (50.4%; range, 4 to 91%) [p < 0.01]. A correction for actual sleep during PSG monitoring reduced the differences between PSG monitoring at home and oximetry monitoring, although a difference in the desaturation time remained (PSG monitoring at home, 31.9% [range, 2 to 75%]; oximetry monitoring, 50.4% [range, 4 to 91%]) [p = 0.041]. A comparison of sleep architectures for nights when PSG was being monitored showed a higher arousal index in the hospital than at home (PSG monitoring in the hospital, 5.6 arousals per hour [range, 2 to 16 arousals per hour]; PSG monitoring at home, 2.5 arousals per hour [range, 1 to 6 arousals per hour]) [p < 0.025], but no differences in SaO(2) levels were found between PSG monitoring at home and PSG monitoring in the hospital. CONCLUSION: The artifacts due to sleep-monitoring equipment may cause an underestimation of the degree of nocturnal hypoxemia in COPD patients. The addition of an unfamiliar environment causes more sleep disruption, but this does not affect nocturnal SaO(2) levels further.

A placebo-controlled clinical trial of regular monotherapy with short-acting and long-acting beta(2)-agonists in allergic asthmatic patients.

BACKGROUND: Some recent studies suggest that regular beta(2)-agonist use may result in inadequate control of asthma. It has been hypothesized that this occurs particularly in allergic asthmatic patients exposed to relevant allergens. Moreover, it is still unclear whether this occurs during the use of both short-acting and long-acting beta(2)-agonists. METHODS: Asthmatic patients (n = 145) allergic to house dust mite (HDM) were randomly allocated to monotherapy with a short-acting beta(2)-agonist (SA; n = 48), a long-acting beta(2)-agonist (LA; n = 50), or placebo (n = 47), double blind, double dummy. The study covered three periods: (1) a 4-week run-in period, in which no changes took place; followed by (2) cessation of treatment with asthma medication including inhaled corticosteroids, introduction of allergen avoidance measures (active/placebo treatment) to lower HDM exposure in the active group, and an 8-week washout period to adjust patients to these changes; followed by (3) a 12-week study medication period. At the start of the 12-week medication period, and every 4 weeks thereafter, spirometric measurements (FEV(1) and provocative concentration of histamine causing a 20% fall in FEV(1) [PC(20)]) were performed. Peak flow and asthma symptoms were recorded daily. Additionally, at the start and every 6 weeks thereafter, dust samples were collected from mattresses and living room and bedroom floors to assess HDM (der p 1) concentrations. Effects on FEV(1), PC(20), peak flow, and asthma symptoms were analyzed with repeated-measurement analysis and corrected for the exposure to HDM allergens. RESULTS: There were no significant differences among the three medication groups after 12 weeks for FEV(1). However, a significant decrease in mean FEV(1) percent predicted (95% confidence interval [CI]) was observed within the SA group: - 6.6 (- 10.4 to - 2.8) (p = 0.0002). A decrease in geometric mean PC(20) (95% CI) of - 1.2 (- 1.96 to - 0.44) doubling concentration was observed within the SA group (p = 0.05). No significant changes in FEV(1) and PC(20) were observed > 12 weeks within the LA group or the placebo group. There were neither changes in peak flow and asthma symptom scores among the three medication groups nor within the groups. Moreover, none of the parameters showed interactive effects with allergen exposure. CONCLUSION: There were no significant differences among the three medication groups for FEV(1) and PC(20). The within-treatment group comparison showed a significant small decline in FEV(1) for the SA group (but not for the LA group), which could indicate that monotherapy with SAs might have negative effects on FEV(1). This was not seen during regular use of LAS: No clear pathophysiologic mechanism can explain these findings at the moment. Relatively high or low exposure to allergens did not alter these findings.

Extrafine beclomethasone dipropionate breath-actuated inhaler (400 micrograms/day) versus budesonide dry powder inhaler (800 micrograms/day) in asthma.

Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol breath-actuated inhaler (Qvar Autohaler; BDP-AH) provides an alternative to chlorofluorocarbon metered dose inhalers or dry powder inhalers (DPIs). The aim of this six-week, open-label study was to determine whether BDP-AH demonstrates equivalent asthma control to twice the dose of budesonide (BUD)-DPI (Pulmicort Turbuhaler). Adults with symptomatic asthma inadequately controlled on BUD-DPI 400 micrograms/day and beta-agonist were enrolled. Patients (n = 193) were randomised to receive 400 micrograms/day BDP-AH (n = 98) (two puffs of 100 micrograms/actuation inhaler twice daily) or 800 micrograms/day BUD-DPI (n = 95) (two puffs of 200 micrograms/actuation inhaler twice daily). Both groups showed a statistically significant change from baseline in morning (a.m.) peak expiratory flow (PEF) at weeks 5-6 (p < 0.01), indicating study treatment improved a.m. PEF over prestudy 400 micrograms/day BUD. Changes from baseline in a.m. PEF at weeks 5-6 were 15.9 l/min for BDP-AH and 14.2 l/min for BUD-DPI; the groups were statistically equivalent (90% CI -7.02-10.44; p < -0.001 [equivalence = within +/- 25 l/min]). Other efficacy assessments (evening PEF, FEV1, asthma symptoms, beta-agonist use) confirmed the treatments were clinically equivalent. Thirty-nine (40%) patients on BDP-AH and 35 (37%) on BUD-DPI experienced at least one adverse event (p = 0.767). Four (4%) patients on BDP-AH and 3 (3%) on BUD-DPI reported increased asthma symptoms. BDP-AH at half the daily dose provided equivalent asthma control to BUD-DPI; both treatments were well tolerated.

Effect of acute metabolic acid/base shifts on the human airway calibre.

Acute metabolic alkalosis (NaHCO(3)), acidosis (NH(4)Cl), and placebo (NaCl) were induced in 15 healthy volunteers (12 females, median age 34 (range 24-56) years) in a double blind, placebo controlled study to evaluate the presence of the effects on airway calibre. Acid-base shifts were determined by capillary blood gas sampling. Measurements were performed at the maximal acid-base shift, 90 min after intervention. Airway resistance (R(aw)) and specific airway conductance (sG(aw)), were evaluated, as primary variables, pre and post intervention. Secondary variables, including bronchial responsiveness to histamine, maximal respiratory mouth pressures and grip strength, were evaluated post intervention. In alkalosis, base excess (BE) increased from -0.3 (-3.0-1.9) to 3.0 (1.0-4.8) mmol/l and pH increased from 7.41 (7.37-7.43) to 7.44 (7.39-7.47) (both P<0.01), accompanied by an increase in Pa(CO(2)): 4.7 (4.0-5.7) to 5.0 (4.7-6.1) kPa (P<0.05). R(aw) increased from 0.156 (0.134-0.263) to 0.169 (0.132-0.271) kPa s/L (P<0.05), sG(aw) decreased, but this was not statistically significantly. In acidosis, BE decreased from -0.2 (-2.0-2.2) to -3.5 (-6.3-1.1) mmol/l and pH decreased from 7.41 (7.39-7.45) to 7.36 (7.31-7.40) (both P<0.01), accompanied by a non-significant decrease in Pa(CO(2)). Changes in R(aw) and sG(aw) were contrary to those in alkalosis, but did not reach statistical significance. Acute metabolic acid-base shifts mildly influence the airway calibre in healthy human subjects.

[Primary liver cell carcinoma as complication of alpha 1-antitrypsin deficiency in a 67 year old man]. / Primair levercelcarcinoom als complicatie van alpha 1-antitrypsinedeficiëntie bij een 67-jarige man.

A 67-year-old male patient with pulmonary emphysema was diagnosed with liver cirrhosis. Further investigations revealed an alpha 1-antitrypsin deficiency caused by a PiZZ mutation. The liver cirrhosis was complicated by the development of a hepatocellular carcinoma. The patient died from the consequences of mesentary vein thrombosis. The protease inhibitor alpha 1-antitrypsin controls the tissue damaging effects of proteases which are produced by granulocytes. In the case of alpha 1-antitrypsin deficiency, progressive damage of the lung tissue occurs, resulting in emphysema. The accumulation of abnormal alpha 1-antitrypsin in hepatocytes can result in cirrhosis, with an increased chance of carcinoma. The deficiency is caused by a mutation in the Pi-gene on chromosome number 14. Although treatment options are at present limited, making an early diagnosis has important implications for the prognosis and intended management with respect to the prevention of complications, both in the patient as well as in first degree relatives (children and siblings).

Volumetric measurements of peripheral oedema in clinical conditions.

Water-displacement volumetry can be used for quantifying the volume of the leg. However, not much is known about its application in patients with peripheral oedema of cardiopulmonary origin. We measured the reproducibility of a water-displacement apparatus with a solid object and in ten non-oedematous clinical patients (group A). The day-to-day variability of the leg volume was assessed in the same group. The diurnal variability was assessed in ten patients with persisting peripheral oedema (group B). The effect of treatment on the severity of peripheral oedema was evaluated in another nine patients with peripheral oedema, who were in need of diuretic treatment (group C). Volumetric results were compared to the ankle circumference method and the body weight method. The coefficient of variation was 0.16% in the fixed object and 0.47% in group A. The day-to-day variability was 1.52% after 1 day and 1.76% after a mean interval of 4.8 days. In group B, leg volume and circumference increased during the day (5.9%, P<0.001, and 2.4%, P<0.01, respectively), while body weight remained unchanged. In group C, leg volume, circumference and body weight decreased significantly after treatment (13.1%, P<0.01, 7.1%, P<0.05, and 5.9%, P<0.05). The correlation between the changes in volume and body weight was poor (r=0.37, P=0.33). In conclusion, (1) water-displacement volumetry is highly reproducible, (2) a diurnal variability of peripheral oedema was found, and (3) volumetry is a suitable tool for monitoring peripheral oedema, while the body weight method appears to be less accurate.

[Use of noninvasive mechanical ventilation to avoid intubation during acute respiratory insufficiency]. / Niet-invasieve beademing ter voorkoming van intubatie tijdens acute respiratoire insufficiëntie.

OBJECTIVE: To determine the value of noninvasive mechanical ventilation in patients with acute respiratory insufficiency. DESIGN: Descriptive. METHODS: Noninvasive mechanical ventilation was considered in all patients with acute respiratory insufficiency in the intensive care unit of the Rijnstate Hospital, Arnhem, the Netherlands, between 1 June 1998 and 31 January 1999. Indication for mechanical ventilation was: respiratory frequency > or = 28/min, and PaCO2 > 6.0 kPa, pH < 7.35, and/or PaO2 < 8.0 kPa. Patients were intubated immediately in case of systolic blood pressure < 90 mmHg, cardiac or respiratory arrest, coma or a severely diminished consciousness. The other patients received noninvasive mechanical ventilation by nasal or full face mask (pressure support: 10-20 cmH2O; positive end expiratory pressure (PEEP): 0-5 cmH2O). Patients were intubated if the respiratory frequency or the level of consciousness or a blood gas value deteriorated. RESULTS: Of the 97 patients who needed ventilation support, 67 were immediately intubated. Noninvasive mechanical ventilation was administered in the other 30 (31%) patients, 22 men and 8 women with a mean age of 67 years (SD: 15). Causes for acute respiratory failure were: chronic obstructive pulmonary disease (COPD) (n = 12); pneumonia (n = 6); heart failure (n = 4); and other (n = 8). Median characteristics at baseline in the noninvasive mechanical ventilation group: acute physiology and chronic health evaluation (APACHE) II score: 17 (range: 1-25); respiratory frequency: 30/min (28-59); pH: 7.33 (6.99-7.54); PaCO2: 9.3 kPa (3.2-18.7); PaO2: 7.4 kPa (4.2-13.4); SaO2: 85% (63-95). Intubation was avoided in 9/30 (30%) of all patients and in 7/12 (58%) of the patients with COPD. Intubation was needed in 21/30 patients (70%): in 8/30 (27%) immediately because of clinical deterioration within 2 hours and in 13/30 (43%) after a mean period of stabilisation of 6 hours (2-16). CONCLUSION: Noninvasive mechanical ventilation prevented intubation in over half of the selected patients presenting with acute respiratory failure due to an exacerbation of COPD. The method appears to be less successful in acute respiratory failure due to other causes.

Effects of house dust mite avoidance measures on Der p 1 concentrations and clinical condition of mild adult house dust mite-allergic asthmatic patients, using no inhaled steroids.

BACKGROUND: Exposure to house dust mite (HDM) allergens often results in worsening of asthma. Therefore, avoidance of exposure to HDM allergens is often proposed. Unfortunately, the most effective and feasible avoidance strategy is still not completely assessed. Consequently, we investigated the effects of a combined HDM avoidance strategy on HDM allergen concentrations and clinical condition of allergic, mild asthmatic, patients using no inhaled steroids. METHODS: Asthmatic patients, allergic to HDM, using no inhaled corticosteroids, were randomly allocated to an active (n = 76) or a placebo allergen-avoidance group (n = 81). Avoidance measures consisted of applying Acarosan(R) (placebo: water) to the living room and bedroom floors, and the use of HDM-impermeable covers for mattresses and bedding (placebo: cotton covers for mattresses only). Effects on allergen concentrations (Der p 1), FEV1, bronchial hyperresponsiveness, peak flow parameters and asthma symptom scores were studied during 20 weeks and controlled for the allergic status of the patients. RESULTS: The active covers reduced Der p 1 concentrations to 9.4% (P = 0.0001), and were always significant lower than in the placebo group (P = 0.0002). Acarosan(R) resulted in slight but significant decreases (twofold, P = 0.0001), both on living room and bedroom floors, but concentrations were never significantly lower than the placebo group. Although the combined avoidance strategy resulted in a considerable reduction in allergen load in the active group, no differences were seen between the two groups in any of the clinical parameters during the follow-up period in this group of allergic asthmatics, using no inhaled corticosteroids. Corrections for the allergic status did not alter these results. CONCLUSIONS: The combined avoidance strategy was effective in reducing HDM allergen concentration. This was especially achieved by the allergen-impermeable covers, while the effects of Acarosan(R) were only marginal. However, this allergen reduction was not reflected in a convincing improvement in clinical condition in this group of mild allergic asthmatics, using no inhaled steroids. Perhaps, a longer follow-up period would have resulted in more pronounced effects.

[Open lung biopsy in severely ill patients with unrecognized pulmonary infiltrates]. / Open longbiopsie bij ernstig zieke patiënten met onbegrepen longinfiltraten.

In three patients, a man aged 34 with aids, a woman aged 67 with recurrent major dyspnoea and a woman aged 73 with chronic lymphatic leukaemia, examination revealed progressive dyspnoea while the chest X-rays showed infiltrative lesions in both lungs. In view of the inadequate response to the treatment administered, an open lung biopsy was performed, following which the diagnosis could be made. Adequate treatment was then started and followed by clinical recovery. It is not clear if open lung biopsy carries higher risks of mortality and morbidity than biopsy by means of flexible bronchoscopy. Open lung biopsy more often leads to a classifying diagnosis. For collection of endobronchial or transbronchial biopsy samples in ununderstood diffuse interstitial lung diseases, flexible bronchoscopy is the method of first choice. Open lung biopsy is a justified supplementary examination, at any rate in severely ill, immunocompromised patients who require adequate therapy without delay.

Oscillatory respiratory impedance and lung tissue compliance.

The respiratory impedance was measured by means of the forced oscillation technique (Landser et al.) and the lung tissue compliance was measured with an oesophageal balloon in 30 patients with a wide range of values of lung tissue compliance. According to the model of respiratory impedance of Nagels et al. it is unlikely that the impedance data are markedly affected by the lung tissue compliance. This hypothesis has not been clinically tested yet. The semistatic compliance (Css) or specific compliance (Cspec) were not statistically correlated with any of the impedance data. Consequently the oscillatory respiratory measurements are not systematically influenced by the compliance of the lung tissue during quiet breathing. However, the dynamic compliance and the frequency dependence of the compliance showed a low but significant correlation with the reactance and resonant frequency (varying from r = 0.41, P < 0.05 to r = -0.54, P < 0.01). A significant correlation was found between the frequency dependence of the lung tissue compliance and the frequency dependence of the oscillatory resistance, both being indicative of peripheral airway obstruction (varying from r = -0.54, P < 0.01 for the whole group, to r = -0.75, P < 0.001 for 15 patients with severe peripheral airway obstruction: mean (SD) FEV1 59.5 (24.8)% pred, mean (SD) MEF50 30.9 (25.8)% pred.

Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects.

The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (PCO2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal PCO2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of PCO2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented.

Variations of respiratory impedance with lung volume in bronchial hyperreactivity.

The total respiratory impedance was measured at various frequencies (4 to 52 Hz) with a pseudo-random-noise forced oscillation technique (FOT). The apparatus (Oscillaire) was connected with a spirometer forming a closed respiratory circuit in which gas concentrations were kept constant. Measurements were made in 15 healthy subjects (group 1) and in 30 asthmatic patients with bronchial hyperreactivity, subdivided into group 2 treated only with inhaled beta 2-mimetics (n = 15) and in group 3 using both beta 2-mimetics and steroids in inhalation (n = 15). No significant differences were found between the impedance data obtained with the Oscillaire alone and those obtained with the Oscillaire connected with the spirometer circuit. The impedance was measured at FRC level, and at FRC +1 L and -1 L. The relative changes of the resistance at 8 Hz were -23.2 percent (13.8) at FRC +1 L and +40.9 percent (29.3) at FRC -1 L relative to the values at resting FRC. This inverse relation between airway resistance and lung volume was similar in all groups. The average reactance decreased at FRC -1 L in all groups. However, at FRC +1 L the average reactance increased 50.6 percent in group 2 and 94.2 percent in group 3, but decreased in group 1. Concomitant changes were observed in the resonant frequency and in the frequency dependence of resistance. Because of these qualitatively different responses of the impedance data to changes in lung volume (both for the whole group and for each individual) between healthy subjects and asthmatic patients, this test might be useful for the diagnosis of bronchial hyperreactivity.