Platelet-activating factor causes ventilation-perfusion mismatch in humans.

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

[Fiber morphometry of the external intercostal muscle. Comparison of dominant and nondominant sides in patients with severe COPD]. / Morfometría fibrilar del músculo intercostal externo. Comparación entre los lados dominante y no dominante en pacientes con EPOC severa.

The general morphometric characteristics of the external intercostal muscle (EIM) of patients with chronic respiratory disease have been well described. Because this muscle is highly accessible, it can provide an ideal model for longitudinal studies using consecutive biopsies of both sides. Whether or not the EIM fiber phenotype is homogeneous on dominant (D) and non dominant (ND) sides is unknown, however. To evaluate possible structural differences in right and left EIM in patients with COPD, eight patients (63 +/- 7 years of age) were enrolled. Lung function, respiratory muscle power, general muscle power and nutritional state were evaluated. Biopsies of the fifth EIM were taken from both sides. Specimens were processed in parallel manner to determine conventional morphometry (hematoxylin-eosin staining), including minimum diameter (Dm) and fiber area (Ar) in cross sections. Fibers were typed by ATPase (at pH 4.2, 4.6 and 9.4) and NADH-TR staining. Nutrition was normal in all patients. All patients had severe COPD (FEV1 27 +/- 7% of reference, limits 13 to 38% of reference) with air entrapment (RV 163 +/- 36% of reference, limits 181 to 276% of reference). None of the patients showed respiratory insufficiency at rest (PaO2 72 +/- 7 mmHg). Peripheral musculoskeletal power measured by manual dynamometer showed no significant right-left differences: D 29 +/- 2 and ND 28 +/- 3 dynes. Morphometric study of 16 muscle specimens showed no significant differences between fiber size on D and ND sides. DmD was 47 +/- 10 microns and ArD, was 2,595 +/- 1,249 microns2. DmD was 49 +/- 9 microns and ArD was 2,636 +/- 953 microns2. Likewise, no significant differences were found between D and ND fiber types: type ID 51 +/- 4% and type IID 49 +/- 5% versus type IND 52 +/- 4% and type IIND 48 +/- 4%. EIM on N and ND sides is homogeneous at the fifth intercostal space. This finding, along with the scarcely invasive nature of the technique for collecting specimens leads us to suggest that longitudinal studies might be performed on the structural effects of various pharmacological or physical treatments followed by COPD patients

[Respiratory muscle force and resistance in patients with SAHS. The effect of using nighttime CPAP]. / Fuerza y resistencia de los músculos respiratorios en pacientes con SAHS. Efecto de la aplicación nocturna de CPAP.

UNLABELLED: During nighttime episodes of obstructive apnea in patients with sleep apnea-hypopnea syndrome (SAHS), repeated and progressive inspiratory efforts are made. Such intense nighttime activity can have a deleterious effect on daytime function of respiratory muscles. OBJECTIVE: The objective of this study was to evaluate daytime respiratory muscle function in a group of SAHS patients before and after two months of treatment with nighttime continuous positive airway pressure (CPAP). METHODS: We enrolled 12 patients with SAHS and 10 normal subjects (control group). To evaluate respiratory muscle strength we measured maximum esophageal pressure (Pesmax), transdiaphragmatic pressure (Pdimax) and inspiratory pressure in the mouth (PM). Respiratory muscle resistance was assessed using peak pressure in the mouth (PMPeak), time of tolerance (Tlim) and maximum inspiratory pressure-time index (PTimax). We also analyzed the nighttime function of respiratory muscles during apneic episodes in 10 of the 12 SAHS patients. We propose and define an index of nighttime respiratory muscle activity (RMian) as the product of the tension-time index for the diaphragm observed at the end of nighttime apneic episodes (TTdiapnea) and the apnea-hypopnea index (AHI). RESULTS: Respiratory muscle strength was similar in the two groups and no changes were observed in SAHS patients after treatment with nighttime CPAP. However, tolerance was lower in SAHS patients (PMpeak--30%, Tlim--31% and PTimax--49%). Two months of nighttime CPAP normalized all three variables in these patients. MRian was related to percent improvement in PMpeak after treatment with nighttime CPAP in SAHS patients (r = 0.66, p < 0.04). CONCLUSION: SAHS has an adverse effect on the daytime endurance of respiratory muscles that is proportional to the increase of nighttime mechanical muscle activity. The application of nighttime CPAP is restorative, probably because it allows respiratory muscles to rest.

[Enteritis caused by Isospora belli in patients with the acquired immunodeficiency syndrome. Description of 9 cases]. / Enteritis por Isospora belli en pacientes con síndrome de inmunodeficiencia adquirida. Descripción de nueve casos.

The features of the nine first cases of Isospora belli enteritis in patients with acquired immunodeficiency syndrome (AIDS) diagnosed in the Hospital Cliníc i Provincial of Barcelona from September 1984 to May 1989 are reported. All patients were male, five were homosexual and four were parenteral drug abusers. The clinical presentation was watery diarrhea without pathological products lasting for more than one month. Five patients had features of dehydration, five had malabsorption, two had fever and one had metabolic acidosis. Enteritis by I. belli was the first opportunistic infection in eight of the nine cases. The number of T4 lymphocytes was lower than 0.4 x 10(9)/l in four of the seven patients in whom it was measured, and the p24 antigen was detected in serum in three out of five. The response to co-trimoxazole, both in the acute phase and as maintenance therapy, was satisfactory; however, two patients had recurrences despite maintenance therapy with co-trimoxazole. In one of them I. belli was clinically resistant to co-trimoxazole therapy and to other drugs, the diarrhea only responding to the administration of a somatostatin analogue (SMS 201-995).

[Skill in the handling of aerosols by health care personnel]. / Destreza en el manejo de los aerosoles por parte del personal sanitario.

Aerosol bronchodilators are extensively used in bronchial asthma treatment and other obstructive pulmonary diseases. Its therapeutic efficacy is closely related to a correct administration technique. We present the results obtained in a prospective study on the skill in the use of the health care professionals in our hospital. A total of 127 physicians and nurses were interviewed, being 110 finally included in the study. Only 22.7% of them used the aerosol correctly and we did not find significant differences between the three groups into which we divided the study (Staff physicians, Residents, and nurses). The most frequently found mistakes were not maintaining as correct apnea after inhalation (62.7%) and not shaking the aerosol before use (48.2%). Up to a 57.2% of those interviewed made two or more of the evaluated mistakes. We conclude that although aerosol bronchodilators and corticoids are extensively prescribed, the lack of knowledge about their correct use by health care professionals is very high, and this could contribute to their misuse by patients under their care.

Evaluation of nasal prongs for estimating nasal flow.

Nasal prongs (NP) connected to a pressure transducer have been suggested as a useful alternative for measuring nasal flow in sleep apnea/hypopnea patients. However, flow measured with NP is expected to be nonlinear. The aim of the present study was to analyze and correct the nonlinearity of nasal flow measurements with NP (VNP). Nasal flow was simultaneously measured with a pneumotachograph (PNT; V) and (NP; VNP) in six healthy subjects during 60 s of breathing at different tidal volumes. Nonlinearity of VNP was assessed by fitting separately, for inspiration and expiration, a Rorher-model equation (VNP x K1 x V + K2 x V2). In addition, we fitted the data to a simpler nonlinear quadratic model (P = K x V2). The main findings were: (1) an excellent fit of the Rorher equation to measured data in all cases; (2) although differences in the Rorher equation coefficients between inspiration and expiration were observed, they were not statistically significant; (3) a substantial intersubject variability was found; and finally, (4) the square root of VNP acceptably fitted the nasal flow data measured by PNT (V) in most cases. We conclude that in order to quantitatively assess nasal flow with NP, data should be corrected for their nonlinear pressure-flow relationships and, that the square root of the flow signal measured with NP is the simplest method of correcting for the observed nonlinearity.

Effects of PEEP on VA/Q mismatching in ventilated patients with chronic airflow obstruction.

Recent work in patients with acute respiratory failure (ARF) due to exacerbation of chronic airflow obstruction (CAO) suggests that application of low degrees of positive end-expiratory pressure (PEEP) can improve rather than impair respiratory mechanics, because PEEP replaces intrinsic PEEP (PEEPi). However, the impact of PEEP on pulmonary gas exchange has not been fully investigated. We designed this study to examine the effects of PEEP and those of PEEPi on ventilation/perfusion (VA/Q) mismatching in mechanically ventilated patients with CAO. Eight patients were studied under four conditions: (1) during controlled mechanical ventilation with the ventilatory setting established by the attending physicians (PEEPi-100%), according to standard criteria; (2) after application of PEEP amounting to 50% (PEEP-50%), and then (3) to 100% (PEEP-100%) of the original PEEPi; and finally, (4) after reduction of PEEPi to 50% of the initial value (PEEPi-50%), obtained by increasing expiratory time and decreasing respiratory rate and tidal volume. Respiratory mechanics, hemodynamics, respiratory blood gases, and VA/Q distributions were measured during each ventilatory mode. At low values of PEEP (PEEP-50%) no changes in respiratory mechanics nor in hemodynamics were observed, but PaO2 moderately increased (from 103 +/- 25.2 to 112 +/- 29.6 mm Hg) and PaCO2 slightly decreased (from 42 +/- 3.7 to 40 +/- 3.3 mm Hg) essentially because of an increase in the mean VA/Q ratio (first moment) of both flood flow (Q, from 0.65 +/- 0.28 to 0.78 +/- 0.29) and ventilation (V, from 4.02 +/- 1.55 to 4.93 +/- 2.00) distributions (p < 0.05, each).(ABSTRACT TRUNCATED AT 250 WORDS)

Salbutamol inhibits pulmonary effects of platelet activating factor in man.

Inhaled platelet-activating factor (PAF) provokes considerable pulmonary gas exchange disturbances in normal man and in patients with mild asthma, similar to those observed in acute severe asthma. To further examine the mechanisms involved in PAF-induced ventilation-perfusion (VA/Q) mismatch, eight healthy, non-atopic, nonsmoking subjects were studied after administration of PAF aerosol (24 micrograms). They had been previously treated with inhaled salbutamol (300 micrograms) in a randomized, double-blind, cross-over, placebo-controlled design. After placebo, PAF provoked a fall in total arterial white cell count with a rebound leukocytosis. As shown in a previous study, an overall index of VA/Q inequality (DISP R-E*, 1.64 +/- 0.10) showed a threefold increase (P < 0.006) that accounted for the increase (79%) in AaPO2 (p < 0.04) after PAF, while the respiratory system resistance (Rrs) rose by 16% (p < 0.02). In contrast, after pretreatment with salbutamol inhaled PAF had no effects on pulmonary gas exchange, Rrs, or white cell count; facial flushing and cough were also hindered. The results are consistent with the hypothesis that salbutamol inhibits PAF-induced venoconstriction in both the airway and pulmonary microcirculation.

Inhaled platelet-activating factor worsens gas exchange in mild asthma.

To investigate the potential effects of inhaled platelet-activating-factor (PAF) (12 micrograms) to perturb pulmonary gas exchange in bronchial asthma, six patients (mean +/- SE, 23 +/- 2 yr) with intermittent asthma (FEV1, 90% predicted) were studied before and 5, 15, and 45 min after challenge. Circulating white blood cells, respiratory system resistance (Rrs), systemic and pulmonary hemodynamics, and respiratory and inert pulmonary gas exchange were measured. Five minutes after PAF leukocytes fell, Rrs increased (by 27%). PaO2 decreased (by 15 mm Hg), and AaPO2 increased (twofold) (p < 0.05 each). Ventilation-perfusion (Va/Q) distributions worsened in a pattern similar to that commonly observed in patients with moderate to severe asthma. Dispersions of pulmonary blood flow (log SD Q) and of alveolar ventilation (log SD V), and an overall index of Va/Q heterogeneity (DISP R-E*) increased significantly (123% for DISP R-E*; p < 0.05, each). Gas exchange indices and Rrs were still minimally abnormal at 15 min but returned towards baseline at 45 min. Ventilatory and hemodynamic variables remained unaltered throughout the study. These results suggest that endogenous PAF may be implicated in the arterial blood gas abnormalities shown during exacerbations of bronchial asthma.

Risk factors of readmission to hospital for a COPD exacerbation: a prospective study.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are a leading cause of admission to hospital among men in many countries, although the factors causing exacerbations are largely unknown. The association between readmission for a COPD exacerbation and a wide range of modifiable potential risk factors, after adjusting for sociodemographic and clinical factors, has been assessed. METHODS: Three hundred and forty patients with COPD recruited during an admission for an exacerbation in four tertiary hospitals in the Barcelona area of Spain were followed for a mean period of 1.1 years. Information on potential risk factors, including clinical and functional status, medical care and prescriptions, medication adherence, lifestyle, health status, and social support, was collected at the recruitment admission. A Cox's proportional hazards model was used to obtain independent relative risks of readmission for COPD. RESULTS: During the follow up period 63% of patients were readmitted at least once, and 29% died. The final multivariate model showed the following risk (or protective) factors: > or =3 admissions for COPD in the year before recruitment (hazard ratio (HR)=1.66, 95% CI 1.16 to 2.39), forced expiratory volume in 1 second (FEV(1)) percentage predicted (0.97, 95% CI 0.96 to 0.99), oxygen tension (0.88, 95% CI 0.79 to 0.98), higher levels of usual physical activity (0.54, 95% CI 0.34 to 0.86), and taking anticholinergic drugs (1.81, 95% 1.11 to 2.94). Exposure to passive smoking was also related to an increased risk of readmission with COPD after adjustment for clinical factors (1.63, 95% CI 1.04 to 2.57) but did not remain in the final model. CONCLUSIONS: This is the first study to show a strong association between usual physical activity and reduced risk of readmission to hospital with COPD, which is potentially relevant for rehabilitation and other therapeutic strategies.

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease.

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.

Risk factors for hospitalization for a chronic obstructive pulmonary disease exacerbation. EFRAM study.

Although exacerbation of chronic obstructive pulmonary disease (COPD) is important in terms of health and costs, there is little information about which are the risk factors. We estimated the association between modifiable and nonmodifiable potential risk factors of exacerbation and the admission for a COPD exacerbation, using a case-control approach. Cases were recruited among admissions for COPD exacerbation during 1 yr in four tertiary hospitals of the Barcelona area. Control subjects were recruited from hospital's register of discharges, having coincided with the referent case in a previous COPD admission but being clinically stable when the referent case was hospitalized. All patients completed a questionnaire and performed spirometry, blood gases, and physical examination. Information about potential risk factors was collected, including variables related to clinical status, characteristics of medical care, medical prescriptions, adherence to medication, lifestyle, quality of life, and social support. A total of 86 cases and 86 control subjects were included, mean age 69 yr, mean FEV(1) 39% of predicted. Multivariate logistic regression showed the following risk (or protective) factors of COPD hospitalization: three or more COPD admissions in the previous year (odds ratio [OR] 6.21, p = 0.008); FEV(1) (OR 0.96 per percentual unit, p < 0.0005); underprescription of long-term oxygen therapy (LTOT) (OR 22.64, p = 0.007); and current smoking (OR 0.30, p = 0.022). Among a wide range of potential risk factors we have found that only previous admissions, lower FEV(1), and underprescription of LTOT are independently associated with a higher risk of admission for a COPD exacerbation.

Bacterial infection in exacerbated COPD with changes in sputum characteristics.

We examined the risk factors for bacterial exacerbation, defined as the presence of pathogenic bacteria in sputum, in 90 chronic obstructive pulmonary disease (COPD) patients with an exacerbation and changes in sputum characteristics. Smoking, alcohol, lung function, body mass index, medical visits and treatments were the independent variables assessed using multivariable logistic regression modelling (OR, 95% CI). A bacterial exacerbation was diagnosed in 39 (43.3%) of 90 patients. Bacterial exacerbations were more prevalent among current smokers (OR 3.77, 95% CI 1.17-12.12), in patients with poor compliance with inhalation therapy (OR 3.25, 95% CI 1.18-8.93) and with severe lung function impairment (FEV1 OR 0.96, 95% CI 0.93-1.00). Prior use of antibiotics was a risk factor for Pseudomonas aeruginosa infection (OR 6.06, 95% CI 1.29-28.44) and influenza vaccination appeared to have a protective effect against this infection (OR 0.15, 95% CI 0.03-0.67). We conclude that severe impairment of lung function, smoking and poor compliance with therapy are risk factors for bacterial infection in COPD, and P. aeruginosa should be suspected in patients who have been treated with antibiotics and in those not vaccinated against influenza.

Adjustment of DLCO for hemoglobin concentration.

The equation proposed by Cotes and coworkers is currently considered as the most acceptable to correct carbon monoxide diffusing capacity (DLCO) for hemoglobin concentration [Hb] by both the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines for standardization of DLCO. In a previous study on 24 anemic patients undergoing bone marrow transplantation (1), we found that DLCO is underestimated using the equation of Cotes and coworkers. To further explore this finding, 28 anemic patients ([Hb] = 8.2 +/- 1.0 (SD) g/dl) with chronic renal failure were prospectively studied during the recovery period of anemia (5.4 +/- 3.5 mo). In all 28 subjects, the slope deltaDLCO/delta[Hb] computed as ratio of overall change in DLCO to overall change in [Hb] throughout the study period was 1.40 +/- 0.72 ml CO/min/mm Hg/g/dl. The individual relationship between measured DLCO and [Hb] closely fitted a simple linear regression. The resulting equations for adjustment of DLCO (DLCOadj) to a standard [Hb] of 14.6 g/dl for men and 13.4 g/dl for women are: [equations: see text]. The present adjustment function for DLCO is linear and independent of the observed DLCO values, whereas the formulas previously proposed are curvilinear, DLCO correction varying with the measured DLCO values. For a measured DLCO of 15 ml CO/min/mm Hg and [Hb] ranging from 7 to 12 g/dl, the present DLCO adjustment is higher (by 2.7 ml CO/min/mm Hg, on average) than that proposed by Cotes and coworkers. This difference appears to be relevant for a precise interpretation of DLCO in patients with normocytic anemia in different clinical conditions.

Función de los músculos respiratorios en el síndrome de apneas-hipopneas durante el sueño / Function of respiratory muscles in sleep apnea-hypopnea syndrome

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