Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep.

OBJECTIVE: To identify the spectrum of respiratory disturbances during sleep in patients with obesity hypoventilation syndrome (OHS) and to examine the response of hypercapnia to treatment of the specific ventilatory sleep disturbances. DESIGNS AND METHODS: Twenty-three patients with chronic awake hypercapnia (mean [+/- SD] PaCO(2), 55 +/- 6 mm Hg) and a respiratory sleep disorder were retrospectively identified. Nocturnal polysomnography testing was performed, and flow limitation (FL) was identified from the inspiratory flow-time contour. Obstructive hypoventilation was inferred from sustained FL coupled with O(2) desaturation that was corrected with treatment of the upper airway obstruction. Central hypoventilation was inferred from sustained O(2) desaturation that persisted after the correction of the upper airway obstruction. Treatment was initiated, and follow-up awake PaCO(2) measurements were obtained (follow-up range, 4 days to 7 years). RESULTS: A variable number of obstructive sleep apneas/hypopneas (ie, obstructive sleep apnea-hypopnea syndrome [OSAHS]) were noted (range, 9 to 167 events per hour of sleep). Of 23 patients, 11 demonstrated upper airway obstruction alone (apnea-hypopnea/FL) and 12 demonstrated central sleep hypoventilation syndrome (SHVS) in addition to a variable number of OSAHS. Treatment aimed at correcting the specific ventilatory abnormalities resulted in correction of the chronic hypercapnia in all compliant patients (compliant patients: pretreatment, 57 +/- 6 mm Hg vs post-treatment, 41 +/- 4 mm Hg [p < 0.001]; noncompliant patients: pretreatment, 52 +/- 6 mm Hg vs post-treatment, 51 +/- 3 mm Hg; [difference not significant]). CONCLUSIONS: This study demonstrates that OHS encompasses a variety of distinct pathophysiologic disturbances that cannot be distinguished clinically at presentation. Sustained obstructive hypoventilation due to partial upper airway obstruction was demonstrated as an additional mechanism for OHS that is not easily classified as SHVS or OSAHS.

Duration of asthma and physiologic outcomes in elderly nonsmokers.

Airway and alveolar inflammation have been described in asthma. Prolonged inflammation may lead to airway remodeling, which can result in physiologic abnormalities. Elderly lifetime nonsmokers are an ideal population in which to examine the consequences of longstanding asthma. To test the hypothesis that airflow limitation and hyperinflation are associated with the duration of asthma, we evaluated airflow and lung volumes in a cohort of elderly asthmatic individuals. All subjects were > 60 yr of age and were lifetime nonsmokers (n = 75). Patients with asthma of long duration (LDA; n = 38) had asthma for >/= 26 yr (median = 40.0 yr); patients with asthma of short duration (SDA; n = 37) had asthma for < 26 yr (median = 9 yr). Patients with LDA had a significantly lower FEV(1)% predicted than did those with SDA (59.5 +/- 2.6% versus 73.8 +/- 3.1% [mean +/- SEM], respectively; p < 0.007). Regression analysis demonstrated that duration of asthma was inversely associated with FEV(1)% predicted (r = 0.264, p < 0.03). After bronchodilator administration, the patients with LDA continued to show airflow obstruction (FEV(1)% predicted = 65.4 +/- 2.9). Only 18% of patients with LDA attained a normal postbronchodilator FEV(1), whereas 50% of those with SDA were able to do so (p < 0.003). The FRC% predicted was significantly higher in subjects with LDA than in those with SDA (142.9 +/- 5.6 versus 124.1 +/- 4.4, respectively, p < 0.01). Multiple regression analysis revealed an association between FRC and duration of asthma that was independent of the degree of airflow limitation. These data suggest that the duration of asthma is associated with the degree of airflow limitation and hyperinflation. Moreover, these abnormalities can become irreversible over time, and may reflect distal airway and/or parenchymal changes as well as proximal airway remodeling.

Frequency dependence of compliance in the evaluation of patients with unexplained respiratory symptoms.

Frequency dependence of compliance (FDC) reflects non-homogeneous ventilatory distribution and, in the presence of a normal measured airway resistance, suggests peripheral airways dysfunction. This study evaluated peripheral airway function and bronchial reactivity in irritant exposed or non-exposed individuals with normal routine pulmonary function tests (PFTs) who had persistent unexplained lower respiratory symptoms. Twenty-two patients were identified with persistent respiratory symptoms and with normal chest X-ray and PFTs. Twenty were non-smokers; two had stopped smoking more than 10 years before evaluation. Twelve patients had been exposed to irritants in their workplaces or at home. Non-specific bronchial hyper-reactivity (nsBHR) and FDC, pre- and post-bronchodilator, were measured in all patients. Studies were repeated in 6/12 irritant-exposed subjects after exposure removal and inhaled corticosteroid treatment. Whereas 12/22 patients had nsBHR, all 22 subjects demonstrated FDC [dynamic lung compliance/static lung compliance Cdyn,1 / Cst,1 at respiratory frequency 60 min(-1) (f60), mean 46%, range 27-67%]. After bronchodilator administration, a 15% improvement Cdyn,1 was observed most consistently at f60 (mean% improvement 26%, 95% CI 14-38%) and in subjects without nsBHR. However, Cdyn,1 at f60 did not return to normal after inhaled bronchodilator. Irritant-exposed and unexposed individuals appeared similar in results of testing for FDC and nsBHR. FDC and its response to bronchodilators provide objective physiological measures of an airway abnormality which may provide a basis for clinical symptoms in patients with normal routine pulmonary function studies. The presence of persistently abnormal FDC after bronchodilator (BD) and on follow up studies may reflect chronic inflammatory and/or structural changes in the airways in addition to bronchoconstriction.

CO(2) homeostasis during periodic breathing in obstructive sleep apnea.

The contribution of apnea to chronic hypercapnia in obstructive sleep apnea (OSA) has not been clarified. Using a model (D. M. Rapoport, R. G. Norman, and R. M. Goldring. J. Appl. Physiol. 75: 2302-2309, 1993), we previously illustrated failure of CO(2) homeostasis during periodic breathing resulting from temporal dissociation between ventilation and perfusion ("temporal V/Q mismatch"). This study measures acute kinetics of CO(2) during periodic breathing and addresses interapnea ventilatory compensation for maintenance of CO(2) homeostasis in 11 patients with OSA during daytime sleep (37-171 min). Ventilation and expiratory CO(2) and O(2) fractions were measured on a breath-by-breath basis by means of a tight-fitting full facemask. Calculations included CO(2) excretion, metabolic CO(2) production, and CO(2) balance (metabolic CO(2) production - exhaled CO(2)). CO(2) balance was tabulated for each apnea/hypopnea event-interevent cycle and as a cumulative value during sleep. Cumulative CO(2) balance varied (-3,570 to +1,388 ml). Positive cumulative CO(2) balance occurred in the absence of overall hypoventilation during sleep. For each cycle, positive CO(2) balance occurred despite increased interevent ventilation to rates as high as 45 l/min. This failure of CO(2) homeostasis was dependent on the event-to-interevent duration ratio. The results demonstrate that 1) periodic breathing provides a mechanism for acute hypercapnia in OSA, 2) acute hypercapnia during periodic breathing may occur without a decrease in average minute ventilation, supporting the presence of temporal V/Q mismatch, as predicted from our model, and 3) compensation for CO(2) accumulation during apnea/hypopnea may be limited by the duration of the interevent interval. The relationship of this acute hypercapnia to sustained chronic hypercapnia in OSA remains to be further explored.

Mechanism of relief of tachypnea during pressure support ventilation.

Pressure support ventilation (PSV) provides a range of ventilatory support from partial respiratory muscle unloading, where inspiratory work is shared between the patient and the mechanical ventilator, to total respiratory muscle unloading, where inspiratory work is performed solely by the ventilator. This study is designed to determine if minimizing work fully accounts for relief of tachypnea during PSV. We examined respiratory parameters over a range of PSV that includes the crossover from partial to total respiratory muscle unloading. Eight studies were obtained on seven intubated patients in respiratory failure. Ventilation, occlusion pressure (P0.1), and patient inspiratory work (WOBinsp) were measured while PSV was varied. In all patients, WOBinsp decreased as PSV increased. The level of PSV where WOBinsp was minimized was identified; this marked the crossover from partial to total respiratory muscle unloading. Frequency decreased with increasing PSV but remained elevated (range, 22 to 38 breaths/min) at the crossover. Frequency was normalized only at PSV levels 131 to 193% of the levels of pressure at the crossover. Tidal volume (VT) changed little during partial support and averaged 5.9 mL/kg at the crossover. VT increased only on PSV providing total unloading. Six of seven patients exhibited increasing static compliance with increasing VT suggesting alveolar recruitment. P0.1 tracked WOBinsp over the entire range of PSV (r = 0.95, p < 0.001). The normalization of frequency observed above the crossover coincided with increasing VT rather than decreasing work. These observations suggest that reflexes resulting from increased VT and/or alveolar recruitment may have contributed to the normalization of frequency.

Flow limitation as a noninvasive assessment of residual upper-airway resistance during continuous positive airway pressure therapy of obstructive sleep apnea.

Many patients with obstructive sleep apnea syndrome (OSAS), despite therapy with nasal continuous positive airway pressure (CPAP), have persisting daytime somnolence that may be due to a persistently elevated upper-airway resistance associated with electroencephalographic (EEG) arousals. We tested the hypothesis that elevated upper-airway resistance can be inferred from the contour of the inspiratory flow tracing obtained from a conventional CPAP circuit. This may provide a noninvasive method for determining optimal CPAP. Data were collected during a CPAP titration of an upper-airway model and in eight patients with OSAS. Estimated inspiratory resistance was calculated from esophageal pressure, CPAP mask pressure, and inspiratory flow. At high CPAP, resistance was low and inspiratory flow contour was found to be rounded. At low CPAP, resistance was high and flow contour developed a plateau suggesting flow limitation. We also noted that the CPAP pressure at which high resistance developed, and at which flow limitation appeared, showed hysteresis. We conclude that when respiration is stable, the contour of inspiratory flow tracing from a CPAP system can be used to infer the presence of elevated upper-airway resistance and flow limitation. Optimizing flow contour may be an alternative to eliminating apneas in evaluation of the optimal therapeutic level of CPAP in OSAS.

CO2 homeostasis during periodic breathing: predictions from a computer model.

The Bohr/Riley model of CO2 homeostasis describes the relationship between CO2 production, ventilation, and arterial PCO2 and assumes that ventilation and CO2 delivery to the lung are both anatomically and temporally well matched. In contrast to normal breathing, periodic patterns of ventilation show temporal mismatch of ventilation to CO2 delivery. We developed a computer model of lung CO2 clearance that uses CO2 transfer equations to generate iterative solutions for PCO2 in multiple body compartments as a function of time. During continuous ventilatory patterns our model predicts steady-state arterial PCO2 identical to that of the Bohr model. During periodic ventilation, we predict mean PCO2 will be elevated unless mean ventilation is increased above that required by the Bohr model. Waxing and waning tidal volumes, low functional residual capacity, and low capillary blood volume potentiate the hypercapnia. However, if cardiac output oscillates in phase with breathing, hypercapnia is minimized. This analysis suggests a new mechanism for the development of sustained hypercapnia, separate from absolute hypoventilation or the presence of lung disease.

Survival in patients with primary pulmonary hypertension. Results from a national prospective registry.

OBJECTIVE: To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. DESIGN: Registry with prospective follow-up. SETTING: Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. PATIENTS: Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. MEASUREMENTS: At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. MAIN RESULTS: The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. CONCLUSIONS: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources.

Endogenous opiates modulate the postapnea ventilatory response in the obstructive sleep apnea syndrome.

Defense of ventilatory homeostasis against recurrent hypercapnia, hypoxia, and acidosis resulting from apnea in obstructive sleep apnea syndrome (OSAS) is dependent on compensatory mechanisms operative between episodes of airway obstruction. This investigation was designed to examine whether endogenous opiate activity modulates the compensatory ventilatory response to apnea in OSAS. Polysomnography and quantitative measurement of tidal volume was performed in 12 patients with moderate to severe OSAS during a morning nap study before and after intravenous administration of 10 mg of naloxone. Apnea index was not significantly altered. There was a small but significant shortening of apneas (postnaloxone apnea duration, 91.2% of prenaloxone; p = 0.002 by ANOVA). Tidal volume of the first postapnea breath and minute ventilation extrapolated from the first two postapnea breaths, but not frequency, increased significantly after naloxone (postnaloxone first breath volume, 112.7% of prenaloxone value [p = 0.03], with a similar increase for minute ventilation, 115.1% [p = 0.007]). The volume of the first postapnea breath was correlated with the duration of the previous apnea, both before (r = 0.59, p = 0.0001) and after naloxone. Despite this, analysis of covariance with apnea duration as the covariate confirmed a significant independent increase in postapnea breath volume after naloxone (p = 0.001). Naloxone also altered sleep architecture, increasing percent time awake during the study period (prenaloxone, 36.3 +/- 15.6%; postnaloxone, 56.7 +/- 22.4%; p = 0.0003) and decreasing total sleep time and percent time in Stage 1. Furthermore, naloxone increased continuity of awake periods (mean length of awake periods increased from 27.0 +/- 8.4 to 66.0 +/- 66.6 s after naloxone, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute reversible hypoxemia in systemic lupus erythematosus.

OBJECTIVE: To determine the frequency of unexplained reversible hypoxemia in patients with systemic lupus erythematosus and to assess the relation between hypoxemia and elevated plasma levels of complement split products. DESIGN: Cohort study. SETTING: Inpatient and outpatient facilities of the New York University Medical Center/Bellevue Hospital and the Hospital for Joint Diseases. PATIENTS: Case patients were 22 patients hospitalized with disease exacerbation and no evidence of parenchymal lung disease on chest roentgenogram. Four patients with stable disease were followed in the outpatient clinic, and five healthy normal volunteers served as controls. MEASUREMENTS: Plasma levels of complement split products (C3a, factor Bb fragment), alveolar-arterial (A-a) Po2 gradients, and pulmonary function were measured. MAIN RESULTS: Nine episodes of hypoxemia or hypocapnia (mean A-a gradient, 30.4 +/- 4.8 mm Hg) or both (despite normal chest roentgenogram results) were noted in six hospitalized patients (group 1). Gas exchange improved within 72 hours of steroid therapy (mean A-a gradient, 11.6 +/- 4.3 mm Hg; P less than 0.01). These patients had an elevated initial mean C3a level (938.4 +/- 246.8 ng/mL) that decreased within 72 hours (407.8 +/- 80.9 ng/mL; P less than 0.01), concomitant with improved oxygenation. Ventilation-perfusion scans, obtained for four of six group 1 patients, excluded pulmonary emboli. Four hospitalized patients (group 2) had a normal A-a gradient (mean, 7.5 +/- 2.7 mm Hg). The mean C3a level of this group (358.3 +/- 39.2 ng/mL) was lower than that of group 1 (P less than 0.05). Four patients with stable disease (group 3) had a mean A-a gradient and a mean C3a level of 3.3 +/- 2.7 mm Hg and 237.8 +/- 105.7 ng/mL, respectively, similar to values found in five normal volunteers, in whom the mean A-a gradient was 3.7 +/- 1.7 mm Hg and the mean C3a level was 124.8 +/- 9.2 ng/mL. CONCLUSION: A syndrome of reversible hypoxemia, unassociated with parenchymal lung disease, is unexpectedly common in acutely ill, hospitalized patients with systemic lupus erythematosus. The pathogenesis of this syndrome is unclear, although the data are compatible with the hypothesis that hypoxemia may be related to pulmonary leukoaggregation.

Differing effects of the anxiolytic agents buspirone and diazepam on control of breathing.

We compared ventilatory effects of the nonsedating anxiolytic buspirone with those of the sedating anxiolytic diazepam in nine normal men. Resting ventilatory parameters and ventilatory responses to CO2 rebreathing and inspiratory threshold loading were measured before and after placebo, diazepam, and buspirone. Placebo had no ventilatory effects. Diazepam had no effect on resting ventilation but depressed response to CO2. Buspirone had no effect on resting ventilation or CO2 response. During loading, buspirone did not alter the augmentation of mouth pressure; diazepam produced a trend toward less augmentation. Both anxiolytics altered the load compensation response for the group; in particular, an increase in ventilation during loading (seen in three of nine subjects) was suppressed by drug administration. Diazepam also markedly depressed one subject's loaded ventilation below unloaded ventilation. In summary, buspirone did not cause the depression of respiratory center chemosensitivity that was seen with diazepam and produced less depression of load compensation in normal subjects. This suggests that it may be a safer anxiolytic in patients with lung disease.

The acute administration of vasodilators in primary pulmonary hypertension. Experience from the National Institutes of Health Registry on Primary Pulmonary Hypertension.

The hemodynamic responses to acute vasodilator administration were evaluated in 163 patients who were entered into the National Institutes of Health Registry on Primary Pulmonary Hypertension (PPH) between 1981 and 1985. Of a total of 491 drug administrations in these patients, 135 administrations in 104 patients were performed in a manner acceptable to the Registry. A single vasodilator was tried in 79 patients and more than one vasodilator in 25 patients. Two-thirds of the patients were in New York Heart Association Functional Classes III or IV. When the effects of all vasodilators were grouped together, there were significant decreases from baseline in mean pulmonary artery pressure (60 +/- 2 to 57 +/- 2 mm Hg, p less than 0.05) and total pulmonary resistance index (32.5 +/- 1.7 to 25.1 +/- 1.4 mm Hg/L/min/m2, p less than 0.0001), and increases in cardiac index (2.1 +/- 0.1 to 2.7 +/- 0.1 L/min/m2, p less than 0.0001). Mean systemic blood pressure fell (88 +/- 1 to 79 +/- 1 mm Hg, p less than 0.0001), whereas PaO2 was unchanged (70 +/- 3 to 71 +/- 3 mm Hg, p = NS). A fall in total pulmonary resistance greater than 20% was observed in 55% of the adequate drug trials. Adverse effects occurred in 32 of the total 491 patient-drug trials and were generally minor. Hypotension requiring treatment developed in six patients. There were two deaths attributable to vasodilator administration. Patients who died or had hypotension requiring treatment had higher right atrial pressures than did other treated patients (15 +/- 2 versus 9 +/- 1 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Volume adjustment of mechanics and diffusion in interstitial lung disease. Lack of clinical relevance.

Relationships of lung mechanics and diffusion to lung volume were examined in 38 patients with interstitial lung disease to determine whether patterns of reduction relate to severity of disease, distinguish histologic characteristics or predict prognosis for reversibility. Normal volume-related values for both mechanics and diffusion were seen throughout the range of severity of disease. The ratio of mechanics to lung volume did not correlate with the ratio of diffusion to lung volume in the same patient. Volume relationships of mechanics and diffusion failed to distinguish pathologic predominance of fibrosis or inflammation/granulomas. These ratios failed to predict reversibility in patients who had repeated tests. These results suggest that in patients with interstitial lung disease the significance of "volume-adjustment" of mechanics and diffusion should be viewed with caution; these parameters do not appear to contribute to the assessment of pathophysiology or correlate with clinical spectrum of interstitial lung diseases.

Background ventilatory stimulus as a determinant of load compensation.

Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment.

Primary pulmonary hypertension. A national prospective study.

A national registry was begun in 1981 to collect data from 32 centers on patients diagnosed by uniform criteria as having primary pulmonary hypertension. Entered into the registry were 187 patients with a mean age (+/- SD) of 36 +/- 15 years (range, 1 to 81), and a female-to-male ratio of 1.7:1 overall. The mean interval from onset of symptoms to diagnosis was 2 years. The most frequent presenting symptoms included dyspnea (60%), fatigue (19%), and syncope (or near syncope) (13%). Raynaud phenomenon was present in 10% (95% of whom were female) and a positive antinuclear antibody test, in 29% (69% female). Pulmonary function studies showed mild restriction (forced vital capacity [FVC], 82% of predicted) with a reduced diffusing capacity for carbon monoxide (DLCO), and hypoxemia with hypocapnia. The mean (+/- SD) right atrial pressure was 9.7 +/- 6 mm Hg; mean pulmonary artery pressure, 60 +/- 18 mm Hg; cardiac index, 2.3 +/- 0.9 L/min X m2; and pulmonary vascular resistance index, 26 +/- 14 mm Hg/L/min X m2 for the group. Although no deaths or sustained morbid events occurred during the diagnostic evaluation of the patients, the typically long interval from initial symptoms to diagnosis emphasizes the need to develop strategies to make the diagnosis earlier.

Respiratory failure in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia.

Seven patients with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia were studied to define the pathophysiology of their respiratory failure. The patients had fever, cough, dyspnea, hypoxemia, and diffuse infiltrates on chest x-ray. Biopsies revealed a spectrum of alveolar filling, interstitial edema and infiltration, and fibrosis. The patients were studied on mechanical ventilation to assess the effect of positive end-expiratory pressure (PEEP) and supplemental oxygen on shunt fraction. Mean anatomic shunt (measured on 100% oxygen) was 34 +/- 8%, which increased significantly (p less than .001) to 43 +/- 9% when the FIO2 was decreased to 40% to 60% (physiologic shunt), indicating ventilation/perfusion (V/Q) imbalance or impaired diffusion. Increasing PEEP by 9 +/- 2 cm H2O reduced the anatomic shunt to 30 +/- 7% (p less than .01) and the physiologic shunt to 37 +/- 7% (p less than .02). There was a similar decrease in anatomic and physiologic shunts in five studies, a greater decrease in physiologic shunt in four, and a greater decrease in anatomic shunt in two. Evidence of alveolar recruitment with PEEP, measured by an increase in static thoracic compliance, was found in only one study. There was no correlation between the effect of PEEP on compliance and its effect on shunt. The data suggest that in patients with AIDS and P. carinii pneumonia, PEEP can decrease shunt by reducing the anatomic shunt, improving V/Q imbalance, and converting areas of anatomic shunt to areas of low V/Q. P. carinii pneumonia in patients with AIDS can produce a clinical and pathophysiologic pattern similar to that described in the adult respiratory distress syndrome.

Hypercapnia in the obstructive sleep apnea syndrome. A reevaluation of the "Pickwickian syndrome".

The mechanisms of hypercapnia in eight patients with the "Pickwickian" syndrome and obstructive sleep apnea (OSAS) were evaluated pretherapy and posttherapy (tracheostomy in seven patients and chronic nocturnal use of nasal CPAP in one). Four patients (correctors) became eucapnic within two weeks of therapy. Four others (noncorrectors) remained hypercapnic. Neither residual apneas, changes in pulmonary function, change in anatomic dead space, nor changes in ventilatory chemoresponsiveness differentiated the two groups, nor did the last three factors account for return to eucapnia in the correctors. The results indicated two separate mechanisms exist for chronic hypercapnia in OSAS: a critical balance between the ventilation during the time spent awake and hypoventilation due to apneas, a mechanism removed by treatment for obstructive apnea; and sustained hypoventilation independent of the apnea phenomenon and therefore not correctible. The subset of patients with the second mechanism appears to represent the true "Pickwickian" syndrome and can be identified before therapy by measuring a low level of ventilation in the sustained awake state.

Relationship of functional residual capacity to static pulmonary mechanics in chronic obstructive pulmonary disease.

Static pulmonary mechanics may not be the sole determinant of the functional residual capacity (FRC) in the chronic obstructive pulmonary diseases (COPD). To assess the relationship of FRC to pulmonary mechanics, pulmonary function tests such as spirometry, lung volumes, maximum expiratory flow volume curves, and single-breath diffusing capacity were related to compliance measurements in 65 patients with stable COPD. Compliance studies were examined over the range of tidal volume and at maximum lung inflation. The results showed that there was a poor correlation between the degree of hyperinflation at FRC and static compliance in the tidal range. However, there was a highly significant correlation between FRC and static lung mechanics at maximum lung inflation, as well as between FRC and diffusing capacity. Thus, in patients with stable COPD, FRC is a useful guide to static recoil properties of the lung as assessed at maximum lung inflation. Lung compliance measurement in tidal range may not reflect this relationship. An increase in FRC remains a useful index of pulmonary emphysema, even in the presence of chronic airway disease.

CO2 rebreathing and exercise ventilatory responses in humans.

The relationship between the resting response to CO2 rebreathing and the ventilatory response to CO2 production during exercise was examined in 20 healthy untrained male subjects and in six patients with obesity hypoventilation syndrome. Patients were chosen because of a severely reduced response to CO2 rebreathing. There was no correlation between the CO2 rebreathing response and the exercise ventilatory response in the normal subjects, the patients, or in the group considered as a whole. This lack of correlation could not be accounted for by differences in ventilatory and occlusion pressure responses nor by reporting responses as a function of a change in hydrogen ion concentration. The independence of the CO2 rebreathing response and the exercise ventilatory response suggests the CO2 rebreathing response does not measure the relevant parameters of ventilatory control during exercise.

Nasal CPAP in obstructive sleep apnea: mechanisms of action.

Sixteen patients with the obstructive sleep apnea syndrome (OSAS) were studied for 1-2 h while receiving continuous positive airway pressure (CPAP) delivered via a nasal mask. Obstructive apneas were obliterated in all. Eight patients had studies of genioglossal muscle activity (GG EMG) and one patient had computed tomograms (CT) of the upper airway while on nasal CPAP. The GG EMG studies showed two patterns: suppression and augmentation of GG EMG while on CPAP. The CT scan showed the airway to be narrowed while the patient was awake off CPAP. It returned to a normal caliber when CPAP was applied, despite sleep. These results are interpreted to suggest three potential mechanisms of action for nasal CPAP in OSAS: 1) reduced upper airway resistance due to prevention of sleep-induced collapse of the airway; 2) reduced upper airway resistance due to dilatation of the airway by nasal CPAP beyond its dimension in the awake state; and 3) possible stimulation of mechanoreceptors leading to an increase in airway tone while CPAP is applied.