Search

Study objectives: The aims of this study were to comprehensively evaluate the cephalometric features of patients with obstructive sleep apnea syndrome (OSAS), and to elucidate the relationship between cephalometric variables and severity of the apnea-hypopnea index (AHI). Patients: The study population consisted of 62 male patients with OSAS, classified into 33 obese patients (body mass index [BMI] > 27) and 29 nonobese patients (BMI < 27), and 13 male simple snorers (AHI < 5 events per hour). Method and measurements: Diagnostic polysomnography and measurements of 22 cephalometric variables were carried out for all patients and simple snorers. Results: Patients with OSAS in both subgroups showed several significant cephalometric features compared with simple snorers: (1) inferiorly positioned hyoid bone, (2) enlarged soft palate, and (3) reduced upper airway width at soft palate. More extensive and severe soft-tissue enlargements including anteriorly positioned hyoid bone and a longer tongue were found in the obese patients. In the nonobese patients, the anteroposterior distances of the bony nasopharynx and oropharynx were significantly smaller than those of simple snorers and obese patients. Stepwise regression analysis showed that anterior displacement of the hyoid bone and retroposition of the mandible were the dominant overall determinants for AHI in patients with OSAS, and that narrowing of the bony oropharynx and inferior displacement of the hyoid bone were dominant determinants for AHI in nonobese patients. A significant regression model for AHI using cephalometric variables could not be obtained for the obese patients, but the BMI proved to be the most significant determinant. Conclusion: Characteristics of the craniofacial bony structure such as narrowing of the nasopharynx and oropharynx and enlargement of the soft tissue in the upper airway may be important risk factors for the development of OSAS in nonobese patients. In obese patients, the deposition of adipose tissue in the upper airway may aggravate the severity of OSAS. (CHEST 2003; 124:212–218)

Study objectives To clarify the effects of oxygen on exercise performance and pulmonary hemodynamics during exercise in patients with COPD with mild hypoxemia at rest. Design Seventy-five male patients with stable COPD ("pink puffer" type), accompanied by mild hypoxemia (> 60 mm Hg) at rest and with mild (percentage of predicted FEV1 [%FEV1] > 50%, n=16), moderate (%FEV1 > 35% to ≤ 50%, n=25), and severe (%FEV1 ≤35%, n=34) airflow obstruction were recruited from an outpatient clinic. A 6-min walking distance (6MD) test was administered to 75 patients, and the pulmonary hemodynamics of 43 subjects were determined during exercise on a supine bicycle ergometer at 25 W and breathing compressed air and oxygen at 2 L/min. Results Supplemental oxygen resulted in a significant increase in 6MD, except for patients with mild airflow obstruction and mild desaturation. This increase in 6MD produced by oxygen was greater as the restriction of the airflow was more severe, and correlated negatively with %FEV1, but not with Pao2 at rest or exercise hypoxemia. Pulmonary artery pressure (Ppa) and pulmonary artery occlusion pressure (Pop) increased with exercise, while the rates of increase in both types of pressure were significantly higher for severe COPD than for mild COPD and moderate COPD. Oxygen inhalation significantly reduced the increases in Ppa and Pop during exercise in patients with moderate-to-severe COPD, and the effect of oxygen on the increase in Pop correlated positively with airtrapping (vital capacity − FVC). Conclusion These findings suggest that supplemental oxygen benefits patients with COPD with moderate-to-severe airflow obstruction and mild hypoxemia at rest, as reflected in improvement in exercise performance and pulmonary hypertension during exercise.

Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood.We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years.A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P.01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P.01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P.01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P.01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects.These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

Background: The pulmonary Mycobacterium avium-intracellulare (MAI) infection in patients with neither predisposing lung disease nor immunodeficiency is recognized to occur predominantly in older or middle-aged and thin females, and has characteristic chest computed tomography (CT) findings with multiple nodules and bronchiectasis. Objective: To investigate the pathophysiology with and individual of MAI infection with neither predisposing lung disease nor immunodeficiency. The bronchoalveolar lavage (BAL) fluid (BALF) was recovered directly from the affected segments identified by the chest CT. Methods: We performed a pulmonary function test (PFT) and BAL in 15 patients (all females) with MAI infection and 5 normal female volunteers. Results: The residual volume and the slope of phase III (ΔN2) were significantly increased and v̇25 was significantly decreased in the 15 patients compared with the normal control subjects. The patients’ BALF showed significant increases in neutrophils and activated CD4 lymphocytes, proinflammatory cytokines, and neutrophil elastase (NE) compared to those in the controls. We analyzed the PFT and BALF findings, and observed a significant correlation between the ΔN2 and interleukin (IL)-8 concentration (r = 0.65, p < 0.01), IL-8/albumin ratio (r = 0.51, p < 0.05) and NE/albumin ratio (r = 0.57, p < 0.05) in the BALF and ΔN2, respectively. Conclusions: These findings suggest that small airway dysfunction in MAI infection without predisposing lung disease is related to the inflammation probably related to the neutrophil.

Study objectives We examined the effects of glucocorticoids on airway inflammation and its association with the reversibility of airflow obstruction in response to oral glucocorticoid administration in patients with COPD. Patients Twenty-four male patients with smoking-related stable pulmonary emphysema without α 1 -antitrypsin deficiency and nine normal healthy volunteers. Measurements We measured the pulmonary function, the inflammatory cells, and the levels of eosinophil cationic protein (ECP), immunoreactive neutrophil elastase-α 1 -protease inhibitor (NE-α 1 -PI) complex, and interleukin (IL)-8 in sputum induced from patients with pulmonary emphysema in its stable phase before and after treatment with 20 mg oral prednisolone per day for 2 weeks. Results The eosinophil and neutrophil counts and the concentrations of ECP, NE-α 1 -PI complex, and IL-8 in the sputum were significantly increased at baseline. The eosinophil count at baseline was significantly correlated with the reversibility of airflow obstruction following treatment, and the treatment also significantly reduced the eosinophil numbers and ECP level in the sputum. In contrast, the increased neutrophil number and the concentrations of NE-α 1 -PI complex and IL-8 at baseline did not correlate with the reversibility and were not affected by treatment. Conclusions These findings suggest that the eosinophilic inflammation, not neutrophilic inflammation, in the airway is involved in the reversible part of the airflow obstruction in response to glucocorticoids in patients with pulmonary emphysema.

Activated eosinophils play an important role in the pathogenesis of bronchial asthma. In this study, we analyzed the inflammatory leukocyte population and the concentrations of eosinophil cationic protein (ECP) and albumin in induced sputum from patients with mild to severe asthma (n=36), and assessed the findings in relation to the severity of their asthma. Both the eosinophil numbers and the concentrations of ECP in the induced sputum were significantly increased in the patients with asthma compared with those in healthy subjects (n=9). There were significant positive correlations between the ECP levels and both the eosinophil counts (r=0.45) and the albumin concentrations (r=0.53). When the asthmatics were classified as having mild (n=12), moderate (n=14), or severe (n=10) asthma as evaluated by their symptoms and peak expiratory flow rate (PEFR), the ECP levels showed significant increases in accordance with the severity of asthma. The eosinophil counts in the patients with severe asthma were significantly higher than those in the patients with mild and moderate asthma; there was no significant difference between those with mild and moderate asthma. The eosinophil counts and ECP levels were also significantly positively correlated with the mean weekly total symptom scores (r=0.52 and r=0.48, respectively) and negatively with the mean percent PEFR on waking (r=—0.50 and r=—0.65, respectively) recorded for 2 weeks prior to the sputum collection. These findings suggest that the eosinophil activation in the airway is closely linked to the symptoms and airflow obstruction of asthma, and that the ECP concentration in induced sputum could serve as useful marker for evaluating the severity of asthma and monitoring airway inflammation to achieve the optimal control of asthma.

Chest computed tomography (CT) and pulmonary function tests are usually used for the evaluation of emphysema. We performed the present study to evaluate more accurately the relationship between the degree of morphological change and the functional abnormality in emphysema. We used a helical CT apparatus to obtain the CT images both at full inspiration and full expiration. We classed the degree of emphysema into 5 grades (0-4) by visual observation on CT image obtained at the two levels, upper and lower fields, on each side. We assigned each of these grades a visual score. We also calculated the average ratio of CT numbers of each of the lung fields at full expiration to that at full inspiration for each level. We designated this the E/I ratio. We then examined the relationship between the findings acquired by each of these two methods and pulmonary function test results. The visual score showed correlations with FEV1(% predicted) (-0.592, p < 0.0001), RV/TLC(%)(0.425, p < 0.025), and DL(CO)/VA(% predicted)(-0.538, p < 0.0001). The E/I ratio showed correlations with FEV1(% predicted) (-0.620, p < 0.0001), RV/TLC(%)(0.661, p < 0.0001), and DL(CO)/VA(% predicted) (-0.299, p < 0.05). Compared with the E/I ratio, the visual score showed much higher correlation with DL(CO)/VA(% predicted), but the E/I ratio showed stronger correlation with RV/TLC(%) than did the visual score. The visual score may reflect the degree of emphysema, whereas the E/I ratio reflects the air trapping. These findings suggest that the helical CT is useful in the evaluation of emphysematous changes and that the E/I ratio reflects the air trapping.

This study was conducted to investigate whether the changes in the pulmonary diffusing capacity found in individuals with acute mountain sickness (AMS) reflect the early stage of high-altitude pulmonary edema (HAPE). We measured the pulmonary diffusion capacity for carbon monoxide (DCO) by the single-breath method, arterialized capillary blood gas, and spirometry in a group of 32 healthy subjects (24 men, eight women) at an altitude of 2,260 m and after ascent to 4,700 m. Twelve subjects (10 men, two women) had symptoms of AMS (AMS group) by the second day after arrival at 4,700 m, but none had clinical signs of pulmonary or cerebral edema. In the non-AMS group, almost all subjects exhibited an increase in DCO at 2,260 to 4,700 m (delta DCO, 10.7 +/- 1.25 mL/min/mm Hg), while the degree of increase in DCO in the AMS group (n = 12) was significantly lower (delta DCO, 1.26 +/- 1.74 mL/min/mm Hg) than that of the non-AMS group (p0.01). In four of the 12 subjects with AMS who had a high AMS score, DCO decreased from 38.4 +/- 4.5 to 33.2 +/- 5.3 mL/min/mm Hg (delta DCO, -5.84 +/- 1.1 mL/min/mm Hg). The AMS group showed significantly lower vital capacity, forced expiratory flow during the middle half of FVC, PaO2, and a greater alveolar-arterial oxygen pressure difference at 4,700 m compared with the non-AMS group. DCO showed a significant negative correlation with AMS score (r = -0.885) and a positive correlation with PaO2 (r = 0.757) at 4,700 m. These results suggest that the decreased pulmonary diffusing capacity in subjects with AMS reflects the presence of pulmonary gas exchange abnormality, which is probably due to subclinical interstitial edema of the lung.

It has been suggested that respiratory muscle dysfunction plays a major role in the development of acute ventilatory failure in patients with chronic obstructive pulmonary disease (COPD). In this study, we devised a respiratory muscle relaxation maneuver using wedge-shaped wooden plates, with which pressure was exerted on the intercostal and accessory respiratory muscles by hand, or by tapping with a wooden hammer, for 15-20 minutes twice a day. The muscle relaxation maneuver was performed in 5 moderate to severe pulmonary emphysema patients for 4 weeks and in 7 emphysema patients for 6 weeks, and the effects on pulmonary function were examined. After the therapy, inspiratory capacity (IC) and vital capacity (VC) in both the 4 weeks- and 6 weekstreated groups, and the forced expiratory volume in 1 second (FEV1.0) in the 6 weeks-treated group were significantly increased, and CO2 retention had also improved. Daily peak expiratory flow (PEF) showed significant increases from 2 weeks after the initiation of the therapy. These results suggest that the respiratory muscle relaxation maneuver is effective for improving the pulmonary function of pulmonary emphysema patients.(Internal Medicine 35: 756-763, 1996)

We have previously shown that high altitude pulmonary edema-susceptible subjects (HAPE-S) have an accentuated pulmonary vascular response to hypoxia. In this study, we investigated the relationship between plasma endothelin-1 (ET-1) levels and the acute hypoxic pulmonary vascular response in HAPE-S and control subjects. In six HAPE-S and seven healthy subjects, we evaluated acceleration time/right ventricular ejection time (AcT/RVET) using Doppler echocardiography, and measured plasma ET-1 levels by radioimmunoassay (RIA) before and after 5 minutes of breathing 10% oxygen. The HAPE-S showed a significantly increased pulmonary vascular response to hypoxia compared with healthy subjects. However, no statistically significant changes of plasma ET-1 levels were observed before and after hypoxia in both groups. We conclude that the increased pulmonary vascular response to acute hypoxia in HAPE-S may not be related to ET-1 release.

To compare the difference for oxygen transport between Tibetans living for generations at high altitude and acclimatized Han newcomers to high altitude, we measured the ventilatory, circulatory, metabolic, and gas exchange functions during exercise in 17 Tibetans and 19 Hans at the altitude of 3417 m. At maximal effort, the Tibetans, compared with the Hans, showed higher O 2 consumption ( V ˙ o 2 max ) (2.54±0.1 versus 2.10±0.1 liters min −1 , p p −1 , p P −1 ) was higher than that in the Hans (68.0±3.9 liters min −1 ), but the ventilatory equivalent was equal. The anaerobic threshold for absolute O 2 consumption ( V ˙ o 2 AT ) for the Tibetans and Hans was 1.91±0.1 versus 1.45±0.1 liters min −1 , respectively ( p 2 consumption (in % V ˙ o 2 max ) was 76.2±1.5 versus 70.5±2.2, respectively ( p V ˙ o 2 max correlated well with maximal cardiac output. No difference was found in the maximal heart rate between the two groups. Arterial oxygen desaturation from rest to exercise in the Hans (15.3%; 90.3–76.5%) was greater than that in the Tibetans (9.2%; 90.1–81.8%). We conclude that the lifelong exposure to an hypoxic environment has resulted in an increase in oxygen transport and improved aerobic exercise performance.

The objective of this case-control study was to investigate the relationship between periodic breathing (PB) and acute mountain sickness (AMS). Nine volunteers, healthy lowlanders between the age of 20 and 36 years stayed at a simulated altitude of 3700 m (485 Torr) for 24 h in a hypobaric chamber. A sleep study was carried out for more than 6 h. Arterial oxygen saturation (SaO2) was monitored by finger oximetry on all subjects. PB was determined by a polysomnography (EEG, EOG, thoracic movement) in six subjects and was indirectly measured by studying the cyclic change of SaO2 in three other subjects. The severity of AMS was assessed with the Environmental Symptoms Questionnaire. All subjects showed lower SaO2 during sleep than when awake (65.0±6.4% versus 72.6±6.4%, p

Objective This study investigated the effect of hyobaric hypoxia on cognitive function. Methods We recorded the auditory brain-stem response (ABR) and auditory-evoked event-related potentials (ERP) in 7 male subjects during a rapid ascent to a simulated 4500 m altitude from their acclimatized altitude of 610 m. The amplitude and latency of each component of ABR and of ERP were assessed. Results Compared with the values at 610 m, at 4500 m the latencies of both waves I and V of ABR significantly increased, with no change in I–V interpeak latency; and the amplitude of wave I decreased, with no change in the amplitude of wave V. The increase in altitude affected neither the amplitude nor the latency of N100. The P300 latency was prolonged significantly after exposure to hypobaric–hypoxic conditions for 2 h, with no significant change in amplitude. At 4500 m, the P300 latency returned to the baseline value after oxygen was inhaled. Conclusions Our results suggest it is possible to boost cognitive processing by supplying oxygen even when auditory stimulus intensity decreases under hypobaric and hypoxic conditions, and that P300 latency is affected by hypoxic more than hypobaric conditions. Significance This study demonstrated that each component of ABR and the latency of both N100 and P300 are important to record when the effects of hypobaric hypoxia on cognitive function are investigated.

Study objectives A blunted hypoxic ventilatory response (HVR) has been observed in some sufferers of high-altitude pulmonary edema (HAPE), and was proposed as a potential mechanism in its pathogenesis. Tyrosine hydroxylase (TH) is a rate-limiting enzyme in the carotid body responding to hypoxia to synthesize dopamine neurotransmitter to heighten ventilation. The association of constitutional susceptibility to HAPE regarding the blunted HVR aspect with polymorphisms of the TH gene was examined. Design A cross-sectional case control study. Setting Shinshu University Hospital, Matsumoto, Japan. Participants Forty-three subjects with a history of HAPE (HAPE group) and 51 healthy climbers without a history of HAPE (control group). Measurements The (TCAT)n tetranucleotide microsatellite repeats within intron 1 and Met81Val variant in exon 2 of the TH gene were investigated by polymerase chain reaction following either direct sequencing or restriction fragment length polymorphism. The HVR in 21 subjects among the HAPE group was also measured. Results No significant frequency differences could be found in terms of either of the two polymorphisms between the HAPE and control groups. Meanwhile, no relationships were observed between the HVR values of HAPE subjects and the individual alleles in both polymorphisms of the TH gene. Conclusion The genetic susceptibility of HAPE, specifically the blunted HVR in HAPE, is probably not associated with the mutations of the TH gene, implying that these two polymorphisms may not be a sufficient genetic marker for predicting a predisposition to the susceptibility to HAPE.

In twelve patients with severe emphysema who underwent lung volume reduction surgery (LVRS), we assessed the results of dyspnea scale, pulmonary function, 6-minute walk distance (6MD), and thoracic movement prior to and 6 months following LVRS. Postoperatively, forced expiratory volume (FEV1), maximum inspiratory mouth pressures (MIP), maximum expiratory mouth pressures (MEP), maximum voluntary ventilation (MVV), diffusing capacity for carbon monoxide (DLCO), partial pressure of oxygen (PaO2) and 6MD were significantly increased with the decrease in dyspnea scale and lung hyperinflation. Thoracic movement, as assessed by the bilateral lung area ratio of the mid-sagittal dimension of dynamic magnetic resonance imaging (MRI) at full inspiration to that at full expiration, was significantly increased. The improvement in thoracic movement was significantly correlated with the increases in FEV1, MVV, and MIP, and with the decrease in residual volume (RV), and with the improvement in the dyspnea scale. These findings suggest that LVRS is an effective procedure for improving not only the airflow limitation and gas exchange but also the thoracic movement in severe emphysema, and these improvements may contribute to an increase in exercise performance and relief of dyspnea.

This study evaluated small airway dysfunction and emphysematous destruction of lung parenchyma in cigarette smokers, using chest expiratory high-resolution computed tomography (HRCT) and pulmonary function tests (PFT). The degree of emphysematous destruction was classified by visual scoring (VS) and the average HRCT number at full expiration/full inspiration (E/I ratio) calculated in 63 male smokers and 10 male nonsmokers (group A). The Brinkman smoking index (BI), defined as cigarettes x day(-1) x yrs, was estimated. Sixty-three smokers were divided into three groups by PFT: group B1 (n=7), with normal PFT; group B2 (n=21), with diffusing capacity of the lung for carbon monoxide (DL,CO)or = 80% predicted, forced expiratory volume in one second (FEV1)80% pred and/or residual volume (RV)120% pred; and group B3 (n=35), with DL,CO80% pred, FEV180% pred and/or RV120% pred. Heavy smokers (BIor = 600) (n=48) showed a significant increase in emphysema by both VS and E/I. E/I was significantly elevated in both group B2 (mean+/-SD 0.95+/-0.05) and B3 (0.96+/-0.06) compared with group B1 (0.89+/-0.03). VS could not differentiate group B2 (3.9+/-5.0) from B1 (1.1+/-1.6). These findings suggest that the expiration/inspiration ratio reflects hyperinflation and airway obstruction, regardless of the functional characteristics of emphysema, in cigarette smokers.

To clarify the structure and function of the airways in Mycobacterium avium-intracellulare (MAI) infection, we performed pulmonary function tests and high-resolution computed tomography (HRCT) of the thorax in female patients 61 +/- 9 yr of age (n = 12) with pulmonary MAI infection without predisposing lung disease and compared their data with those of normal female volunteers 54 +/- 8 yr of age (n = 9). We calculated the E/I ratio, i.e., the average ratio of HRCT number at full expiration to that at full inspiration, as an index for the evaluation of air trapping distal to the small airways. Patients showed significant increases in residual volume and slope of phase III (DeltaN2) of the single-breath nitrogen test, and significant decreases in flow at 50 and 25% of FVC, suggesting hyperinflation and obstruction of the small airways. HRCT of patients revealed the small nodules and ectasis of bronchioles and small bronchi located mainly in segments (S) S2, S3, S4, and S5. The E/I ratio was significantly elevated in patients, and especially higher in the upper lung field than in the lower lung field, suggesting air trapping distal to the small airways. The difference of E/I ratio between the upper and lower field is probably related to the segmental distribution of CT abnormalities. These findings suggest that MAI infection can lead to air trapping distal to the small airways.

Background —A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. Methods and Results —The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects ( P =.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects ( P =.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6–positive subjects with HAPE was significantly higher than that of the HLA-DR6–negative subjects with HAPE. Conclusions —There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.

We describe a patient with obstructive sleep apnea (OSA) whose apnea-hypopnea index (AHI) improved remarkably in the prone position accompanied by an improved sleep quality, despite a higher AHI in the supine position and even in the lateral position. Magnetic resonance imaging revealed the most dilated upper airway in the prone position, which suggests the role of anatomical narrowing of the upper airway as an important component in the pathophysiology of positional apnea patients. Further studies are needed to determine the therapeutic efficacy of a prone sleeping position in patients with OSA.(Internal Medicine 34: 1190-1193, 1995)

The eosinophil count and concentrations of eosinophil cationic protein (ECP) were measured in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), sarcoidosis, and healthy controls. The patients with IPF and PF-CVD showed significant increased eosinophil count and ECP levels in BALF compared with the controls. When the patients with IPF and PF-CVD were subclassified into chronic stable, progressive, and acute progressive subgroups in accordance with the observed progression of pulmonary dysfunction during the preceding 3- to 6-month period, those in the acute progressive subgroup showed significantly elevated recovered eosinophil count and ECP level, as well as recovered lymphocyte count and total protein, albumin, and type III procollagen aminoterminal peptide-related antigens (pIIIp) in BALF, compared with either of the other two subgroups. Multivariate stepwise logistic regression analysis revealed that, among these variables, only ECP and pIIIp significantly contributed to discrimination among the three subgroups differing in disease activity. These findings suggest that eosinophils are involved in the inflammatory process in pulmonary fibrosis and that the released ECP and other cytotoxic eosinophil products may contribute to the lung injury and development of fibrosis.

To determine the role of neutrophil elastase in asthmatic responses, we studied the effect of ONO-5046, a specific neutrophil elastase inhibitor, on antigen-induced asthmatic responses in allergic sheep. Pulmonary resistance (RL) was measured for 8 h after antigen challenge. Measurements of airway responsiveness to methacholine and bronchoalveolar lavage fluid (BALF) were obtained 8 h after challenge. Antigen challenge caused early and late increases in RL, airway hyperresponsiveness (AHR), and recruitment of neutrophils and eosinophils along with increases in TXB2 and LTB4 in BALF. ONO-5046 treatment significantly reduced both early and late bronchoconstriction, neutrophil recruitment, increases in LTB4 in BALF, and AHR. ONO-5046 post-treatment significantly reduced the increase in RL 8 h after antigen challenge. Another neutrophil elastase inhibitor, FR 134043, significantly reduced both early and late bronchoconstriction. ONO-5046 had little effect on calcium ionophore-induced LTB4 release from isolated neutrophils and whole blood obtained from drug-treated sheep. These findings suggest that neutrophil elastase is involved in antigen-induced bronchoconstriction and AHR mediated by neutrophil accumulation and 5-lipoxygenase products in allergic sheep.

We investigated the effects of acute hypoxia (10% O2) on plasma level of atrial natriuretic peptide (ANP) and pulmonary hemodynamics in five subjects with a history of high-altitude pulmonary edema (HAPE). Plasma renin activity and plasma levels of aldosterone, epinephrine and norepinephrine were also measured. The plasma ANP levels in HAPE-susceptible subjects rose significantly in response to 10% O2 (from 34.8 +/- 5.4 to 51.4 +/- 7.3 pg.ml-1; P less than 0.05), not associated with any increase in either atrial pressure. Compared with six control subjects, the rise of ANP level was greater in HAPE-susceptible subjects (16.6 +/- 4.4 vs 3.9 +/- 1.2 pg.ml-1; P less than 0.05). There was a significant positive correlation between the rise of ANP level and the increase of pulmonary arterial pressure. No significant difference was observed in any of other hormonal responses to acute hypoxia between the two groups. We interpret these results as indicating that the ANP secretory response to acute hypoxia in HAPE-susceptible subjects, which is not mediated by an increase in atrial pressure, may be greater than that in nonsusceptible subjects in association with a greater pressor response of pulmonary circulation.

It is well known that healthy low-altitude residents often develop abnormal breathing pattern and oxygen desaturation during sleep at high altitude, although few studies of sleep during long-term sojourn at high altitude have been conducted. The purpose of this study was to investigate changes in breathing pattan and oxygen desaturation during sleep at high altitude, and their relation to pattern of ascent and descent, as well as to the acclimatization process in low-altitude residents.

We examined, in isolated blood perfused rat lungs, the effect of the cell permeable 8-bromo derivative of cGMP on pulmonary vasoconstriction induced by either alveolar hypoxia or angiotensin II. 8-Bromo cGMP dose-dependently reduced both hypoxia-(IC50 = 2.2 X 10(-5) M) and angiotensin-II-induced pulmonary vasoconstriction (IC50 = 5.0 X 10(-5) M). This effect of 8-bromo cGMP on pulmonary vasoconstriction was not affected by cyclooxygenase blockade. MB 22948 (0.1 mM), an inhibitor of cGMP-phosphodiesterase, reduced synergistically with 8-bromo cGMP the hypoxia or angiotensin-II-induced vasoconstriction. The cGMP-phosphodiesterase inhibitor MB 22948, by itself, selectively reduced hypoxia-induced vasoconstriction, suggesting a modulating effect of endogenous cGMP during hypoxic vasoconstriction.

Study objectives To clarify the effects of lung volume reduction surgery (LVRS) on pulmonary hemodynamics in severe emphysema and to evaluate the role of pulmonary circulation in the increased exercise performance after LVRS. Design In eight male patients with severe emphysema, we measured pulmonary artery (Ppa) and occlusion (Pop) pressures and cardiac output through a Swan-Ganz thermodilution catheter, and we calculated cardiac index (CI), pulmonary vascular resistance index, and driving pressure. The study was performed at rest and during exercise using a supine bicycle ergometer at 25 W, under room air and O 2 inhalation. Exercise performance was expressed as endurance time in minutes. Pulmonary function tests were performed. The patients underwent an identical study before and 6 months after LVRS. Results The patients' exercise performance was significantly increased after LVRS (5.9 ± 1.8 min) compared with that before LVRS (3.6 ± 0.9 min). LVRS resulted in a significant increase in FEV 1 and a significant decrease in residual volume. Before LVRS, Ppa was increased both at rest and during exercise. LVRS did not change rest or exercise Ppa. LVRS significantly decreased Pop during exercise from 24 ± 10 mm Hg to 18 ± 7 mm Hg. CI at rest and during exercise were significantly increased after LVRS. O 2 administration significantly decreased Ppa during exercise both before and after LVRS. Conclusions These findings suggest that LVRS does not improve pulmonary hypertension at rest or during exercise in patients with severe emphysema and that elevated Pop during exercise before LVRS is probably related to lung mechanic abnormalities.

To investigate whether the acute hypoxia can be a stimulus for atrial natriuretic peptide (ANP) secretion, plasma levels of ANP were determined under three different hypoxic conditions in six normal subjects. During 15% O2 breathing for 10 min, no significant change in plasma ANP level was observed. Severe hypoxia induced by 10% O2 breathing increased the mean pulmonary arterial pressure (Ppa) by 11.6 mm Hg within 10 min (P less than 0.01), accompanying a slight but significant rise in plasma ANP level of pulmonary artery (PA) from 24.3 +/- 5.3 to 28.2 +/- 4.6 pg/ml (P less than 0.05). There was a tendency for the ANP level of PA to rise under hypoxic hypobaria at 515 Torr for 10 min, followed by a decrease of that level during 100% O2 breathing under hypobaric condition. These changes, however, still remained in the normal range. No significant changes were observed both in right atrial pressure and in pulmonary capillary wedge pressure under any of the three hypoxic conditions. From these results we conclude that ANP can be released in response to the elevation of Ppa caused by acute hypoxia in normal subjects, but the changes in plasma ANP level may be too small to play a significant physiological role in hemodynamic responses to acute hypoxia.