Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients

BACKGROUND: Pulmonary involvement is the leading cause of systemic sclerosis (SSc)-related deaths. A simple test to evaluate exercise capacity is the 6-min walk test (6MWT), and the walk distance is used as a primary outcome in clinical trials. Hemoglobin desaturation during a 6MWT is predictive of mortality in patients with primary pulmonary hypertension. Our objectives were to evaluate the walk distance and resting oxygen saturation - oxygen saturation after the 6-min period (DeltaSat) during the 6MWT in patients with SSc, and to establish correlations between the 6MWT results and other clinical variables. METHODS: We analyzed 110 SSc patients. DeltaSat was defined as a fall of end-of-test saturation >or= 4%. Clinical and demographic data were collected. All the patients were submitted to chest radiographs and high-resolution CT (HRCT) and underwent pulmonary function testing and echocardiography, and the presence of autoantibodies was determined. RESULTS: The variables associated with a walk distance < 400 m (p < 0.05) were age, dyspnea index, fibrosis on radiography, pulmonary arterial systolic pressure (PASP) >or= 30 mm Hg, and desaturation. The variables associated with DeltaSat (p < 0.05) were age, positive anti-Scl-70 autoantibody, dyspnea index, fibrosis on radiography, FVC < 80% of predicted, PASP >or= 30 mm Hg, and ground-glass or reticular opacities on HRCT. In the multivariate logistic regression analysis, three variables were significant when tested with walk distance: age, race, and dyspnea index; four variables were significant when tested with DeltaSat: age, dyspnea index, positive anti-Scl-70 autoantibody, and FVC < 80% of predicted. CONCLUSIONS: Desaturation during a 6MWT provides additional information regarding severity of disease in scleroderma patients with pulmonary manifestations.     

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.     

Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis

STUDY OBJECTIVES: To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension. DESIGN: Prospective analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization (RHC) and pulmonary function testing (PFT). Pulmonary arterial pressure (PAP) and diffusion capacity of the lung for carbon monoxide (Dlco) were focused on. SETTING: University hospital. PATIENTS: Seventy-eight patients with IPF (67 men, 11 women; diagnosis by pathology, n = 59; clinical diagnosis, n = 19) had been followed up after initial workup for a maximum of 14 years. MEASUREMENTS AND RESULTS: RHC data on 61 patients and PFT data on 52 patients were available. Five-year survival rates were 62.2% in the normal-PAP group (mean PAP < 17 mm Hg, n = 37) and 16.7% in the high-PAP group (mean PAP > 17 mm Hg, n = 24) [p < 0.001]; 70.4% in the preserved-Dlco group (percentage of predicted > 40%, n = 27) and 20.0% in the low-Dlco group (percentage of predicted < 40%, n = 25) [p < 0.001]; and 82.6% in group 1 (normal PAP and preserved Dlco, n = 23) and 15.6% in group 2 (high PAP, low Dlco, or both, n = 32) [p < 0.0001]. The relative risks of mortality within 5 years after RHC were 2.20 (95% confidence interval [CI], 1.40 to 3.45) in the high-PAP group, 2.70 (95% CI, 1.46 to 4.99) in the low-Dlco group, and 4.85 (95% CI, 1.97 to 11.97) in group 2. CONCLUSION: Dlco was a critical factor for evaluating disease status and prognosis, and PAP status provided feasible information in the initial workup of IPF patients.     

Validation of a method to screen for pulmonary hypertension in advanced idiopathic pulmonary fibrosis

BACKGROUND: We have developed a method to screen for pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients, based on a formula to predict mean pulmonary artery pressure (MPAP) from standard lung function measurements. The objective of this study was to validate this method in a separate group of IPF patients. METHODS: Cross-sectional study of 60 IPF patients from two institutions. The accuracy of the MPAP estimation was assessed by examining the correlation between the predicted and measured MPAPs and the magnitude of the estimation error. The discriminatory ability of the method for PH was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: There was strong correlation in the expected direction between the predicted and measured MPAPs (r = 0.72; p < 0.0001). The estimated MPAP was within 5 mm Hg of the measured MPAP 72% of the time. The AUC for predicting PH was 0.85, and did not differ by institution. A formula-predicted MPAP > 21 mm Hg was associated with a sensitivity, specificity, positive predictive value, and negative predictive value of 95%, 58%, 51%, and 96%, respectively, for PH defined as MPAP from right-heart catheterization > 25 mm Hg. CONCLUSIONS: A prediction formula for MPAP using standard lung function measurements can be used to screen for PH in IPF patients.     

Detailed analysis of the radiographic presentation of Mycobacterium kansasii lung disease in patients with HIV infection

BACKGROUND: Published criteria for the diagnosis of Mycobacterium kansasii lung disease require the presence of clinical symptoms, positive microbiologic results, and radiographic abnormalities. In patients with HIV infection, the radiographic findings of M kansasii lung disease are not well described. METHODS: Medical records and chest radiographs of all patients with HIV infection and at least one respiratory specimen culture positive for M kansasii at San Francisco General Hospital between December 1989 and July 2002 were reviewed. RESULTS: Chest radiographic results were abnormal in 75 of 83 patients (90%) included in the study. Radiographic abnormalities were diverse, with consolidation (66%) and nodules (42%) as the most frequent findings. The mid or lower lung zones were involved in 89% of patients. The pattern of radiographic abnormalities did not differ based on acid-fast bacilli smear status, the presence or absence of coexisting pulmonary infections, or CD4+ T-lymphocyte count. In multivariate Cox regression analysis, cavitation was the only radiographic abnormality independently associated with mortality (hazard ratio, 4.8; 95% confidence interval, 1.2 to 19.6). CONCLUSION: Patients with HIV infection and M kansasii lung disease present with diverse radiographic patterns, most commonly consolidation and nodules predominantly located in the mid and lower lung zones. This finding is in contrast to the upper-lobe cavitary presentation described in patients without HIV infection. Although rare, the presence of cavitary disease in patients with HIV infection and M kansasii independently predicts worse outcome. The diversity in the radiographic presentation of M kansasii lung disease implies that clinicians should obtain sputum mycobacterial culture samples from any patient with HIV infection and an abnormal chest radiograph finding.     

Outcomes and safety of surgical lung biopsy for interstitial lung disease

STUDY OBJECTIVES: To determine the safety of surgical lung biopsy (SLB) in patients with interstitial lung disease (ILD), and specifically in those with idiopathic pulmonary fibrosis (IPF). DESIGN: Retrospective cohort. SETTING: Tertiary care university-affiliated military medical center. PATIENTS: Individuals undergoing SLB for suspected ILD. MEASUREMENTS AND RESULTS: We examined outcomes for subjects with a clinical diagnosis of ILD who had been designated to undergo SLB. Mortality (assessed at 30 and 90 days) following SLB represented the primary end point. Morbidity resulting from complications from SLB served as a secondary end point. The cohort included 83 patients (mean [+/- SD] age, 57.3 +/- 14.2 years; men, 57.8%). IPF was eventually diagnosed in slightly more than half of the subjects. Overall, 30-day and 90-day mortality rates were low (4.8% and 6.0%, respectively). Subjects with IPF did well with SLB (30-day mortality rate, 7.1%) and did not face a higher risk of either death or complications relative to individuals with non-IPF forms of ILD. The only predictors of perioperative mortality were either the need for mechanical ventilation (MV) at the time of SLB or being immunosuppressed prior to undergoing SLB. Excluding persons who met either criterion yielded an overall 90-day post-SLB mortality rate of 1.5% in persons with IPF. Approximately 40% of patients in whom IPF was eventually diagnosed were initially thought to have another form of ILD. CONCLUSIONS: Persons with IPF tolerate SLB well. Requiring MV or being immunosuppressed is associated with an increased risk for death following SLB. Safety concerns should not preclude referral for SLB in patients who are clinically suspected of having IPF.     

Prevalence and reversibility of pulmonary dysfunction in refractory systemic lupus: improvement correlates with disease remission following hematopoietic stem cell transplantation

AIM: To report the prevalence and reversibility of pulmonary function test (PFT) abnormalities among systemic lupus erythematosus (SLE) patients, refractory to therapy, undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Thirty-four SLE patients received 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin followed by HSCT. PFTs were performed prior to, at 6 months, and yearly following HSCT. RESULTS: The prevalence of significant PFT abnormalities was high (97%). Low FEV(1) and FVC occurred in 26 of 34 patients (76%). A significant abnormality in diffusion capacity of the lung for carbon monoxide (Dlco) occurred in 26 of 32 individuals able to complete Dlco testing (81%). Dlco 18 months after HSCT. Five of 28 patients had a normal entry FVC; for each, the FVC remains normal. Of the 23 patients with an abnormal baseline FVC, 18 have improved, 15 completely and 3 partially. Eight of these 18 patients also have improved Dlco. The two patients with a diagnosis of SLS and one patient with SLE-related pulmonary hypertension improved in both parameters. Only 5 of 23 patients with an abnormal FVC did not improve. Each of these five patients retained active lupus in spite of HSCT. CONCLUSION: The prevalence of lung impairment among SLE patients requiring long-term immune suppression is high. Following HSCT, pulmonary impairments can improve, which is sustained if disease control is sustained.     

Zinc chloride (smoke bomb) inhalation lung injury: clinical presentations, high-resolution CT findings, and pulmonary function test results

STUDY OBJECTIVES: Zinc chloride smoke inhalation injury (ZCSII) is uncommon and has been rarely described in previous studies. We hypothesized that structural changes of the lung might correlate with pulmonary function. To answer this question, we correlated findings from high-resolution CT (HRCT) scan and the results of pulmonary function tests (PFTs) in patients with ZCSII. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: Twenty patients who had been hospitalized with ZCSII-related conditions. MEASUREMENTS: The study included HRCT scan scores (0 to 100), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (D(LCO)). RESULTS: HRCT scans and PFTs were performed initially after injury (range, 3 to 21 days) in all patients and during the follow-up period (range, 27 to 66 days) in 10 patients. The predominant CT scan findings were patchy or diffuse ground-glass opacities with or without consolidation. The majority of patients showed a significant reduction of FVC, FEV1, total lung capacity, and D(LCO), but normal FEV1/FVC ratio values. Changes of functional parameters correlated well with HRCT scan scores. Substantial improvements in CT scan abnormalities and pulmonary function were observed at follow-up. CONCLUSIONS: The majority of our patients with ZCSII presented with a predominant parenchymal injury of the lung that was consistent with a restrictive type of functional impairment and a reduction in Dlco rather than with obstructive disease. Our results suggest that HRCT scanning and pulmonary function testing may reliably predict the severity of ZCSII.     

Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis

BACKGROUND: Pulmonary hypertension (PH) is commonly seen in patients with idiopathic pulmonary fibrosis (IPF). We sought to examine the relationship between pulmonary function tests (PFTs), including the percentage of predicted FVC (FVC%), percentage of predicted total lung capacity, percentage of predicted diffusing capacity of the lung for carbon monoxide (Dlco%), the composite physiologic index (CPI), and PH. The ability of FVC%, Dlco%, and FVC%/Dlco% ratio to predict underlying PH was assessed. METHODS: Retrospective review of IPF patients seen at a tertiary referral center over an 8-year interval in whom both PFT and right-heart catheterization data were available. RESULTS: The study cohort consisted of 118 patients, of whom 48 patients (40.7%) had PH. There was no correlation between measures of lung volumes or the CPI with underlying PH. There was a modest association between Dlco% and PH, with Dlco% < 30 having a twofold-higher prevalence of PH (56.4%) compared to Dlco% >/= 30 (28.6%). Cardiac dysfunction might have played a small role, since 16.1% of the patients had an associated elevated pulmonary capillary wedge pressure. There was a trend to a higher prevalence and greater severity of PH in those patients with FVC% > 70 compared to the group with FVC% < 40. CONCLUSION: PH is common in patients with IPF. There is a poor correlation between lung function measures and PH, suggesting that factors other than fibrosis may play a role in the etiology. The unexpected high prevalence and severity of PH in patients with well-maintained lung function have implications for the prognosis and management of the disease.     

Predictors of nocturnal oxygen desaturation in pulmonary arterial hypertension

Background:Sleep may be associated with significant respiratory compromise in patients with lung disease and can result in hypoxia. In patients with pulmonary arterial hypertension (PAH), nocturnal desaturation may not be reflected in daytime evaluations of oxygenation and can lead to worsening pulmonary hemodynamics. The study was conducted to determine the prevalence and significance of nocturnal oxygen desaturation in patients with PAH.Methods:A cross-sectional study conducted at the Cleveland Clinic. Patients were followed up at our institution except for the overnight oximetry study done at home. Data regarding degree of nocturnal desaturation, demographics, hemodynamics, pulmonary function, and functional capacity were collected.Results:Forty-three patients (mean age, 47.9 ± 13.5 years [± SD]; 36 women and 7 men) underwent nocturnal oximetry. The etiology of PAH included idiopathic PAH (88%) and PAH associated with connective tissue diseases (12%). The majority of patients were New York Heart Association functional class II (42%) or III (53%). Thirty patients (69.7%) spent > 10% of sleep time with oxygen saturation by pulse oximetry < 90%. Desaturators were older (p = 0.024) and had higher hemoglobin (p = 0.002). Sixteen of 27 patients (59%) without desaturation < 90% during a 6-min walk test were nocturnal desaturators. Nocturnal desaturators had higher brain natriuretic protein (p = 0.004), lower cardiac index (p = 0.03), and higher mean right atrial pressure (p = 0.09), mean pulmonary artery pressure, and pulmonary vascular resistance. On echocardiography, desaturators were more likely to have moderate or severe right ventricular dilation (p = 0.04) and pericardial effusion. Only one patient had significant sleep apnea.Conclusions:Nocturnal hypoxemia is common in PAH patients and correlates with advanced pulmonary hypertension and right ventricular dysfunction. Approximately 60% patients without exertional hypoxia had nocturnal desaturation. Overnight oximetry should be considered in the routine workup of PAH patients who do not demonstrate exertional desaturation.     

Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life

BACKGROUND: To ascertain if analysis of lung density histograms in thin-section CT was more reproducible than visual assessment of lung changes in systemic sclerosis (SSc), and if such density histogram parameters as mean lung attenuation (MLA), skewness, and kurtosis could more closely reflect pulmonary function as well as exercise and quality of life impairment. METHODS: The intraoperator and interoperator reproducibility of visual and densitometric lung CT analysis in 48 SSc patients examined with CT were evaluated by means of weighted kappa statistics. Univariate and multivariate regression analyses were applied to evaluate the relationship of visual and densitometric CT measurements with functional parameters including functional residual capacity (FRC), FVC, FEV(1), diffusion capacity of the lung for carbon monoxide (Dlco), 6-min walking testing (6MWT), and health-related quality of life questionnaire (QLQ) parameters. RESULTS: The intraoperator and interoperator reproducibility of MLA (intraobserver weighted kappa = 0.97; interobserver weighted kappa = 0.96), skewness (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88), and kurtosis (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88) were higher than those of visual assessment (intraobserver weighted kappa = 0.71; interobserver weighted kappa = 0.69). In univariate analysis, only densitometric measurements were correlated with some exercise and QLQ parameters. In multivariate analysis, MLA (square regression coefficient corrected [R(2)c] = 0.70), skewness (R(2)c = 0.78), and kurtosis (R(2)c = 0.77) were predicted by FRC, FVC, Dlco, 6MWT, and QLQ parameters, while visual assessment was associated only with FRC and FVC (R(2)c = 0.40). CONCLUSIONS: In SSc, densitometric analysis is more reproducible than visual assessment of lung changes in thin-section CT and more closely correlated to pulmonary function testing, 6MWT, and QLQ. Density histogram parameters may be useful for cross-sectional and longitudinal studies of lung involvement in SSc.     

Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease

STUDY OBJECTIVES: To investigate the histopathologic pattern and clinical features of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) according to the American Thoracic Society (ATS)/European Respiratory Society consensus classification of idiopathic interstitial pneumonia. DESIGN: Retrospective review. SETTING: Two thousand-bed, university-affiliated, tertiary referral center. PATIENTS: Eighteen patients with RA who underwent surgical lung biopsy (SLBx) for suspected ILD. METHOD: SLBx specimens were reviewed and reclassified by three lung pathologists according to the ATS/European Respiratory Society classification. Clinical features and follow-up courses for the usual interstitial pneumonia (UIP) pattern and the nonspecific interstitial pneumonia (NSIP) pattern were compared. RESULTS: The histopathologic patterns were diverse: 10 patients with the UIP pattern, 6 patients with the NSIP pattern, and 2 patients with inflammatory airway disease with the organizing pneumonia pattern. RA preceded ILD in the majority of patients (n = 12). In three patients, ILD preceded RA; in three patients, both conditions were diagnosed simultaneously. The majority (n = 13) of patients had a restrictive defect with or without low diffusion capacity of the lung for carbon monoxide (D(LCO)) on pulmonary function testing; 2 patients had only low (D(LCO)). The UIP and NSIP groups were significantly different in their male/female ratios (8/2 vs 0/6, respectively; p = 0.007) and smoking history (current/former or nonsmokers, 8/2 vs 0/6; p = 0.007). Many of the patients with the UIP pattern had typical high-resolution CT features of UIP. Five patients with the UIP pattern died, whereas no deaths occurred among patients with the NSIP pattern during median follow-up durations of 4.2 years and 3.7 years, respectively. CONCLUSIONS: The histopathologic type of RA-ILD was diverse; in our study population, the UIP pattern seemed to be more prevalent than the NSIP pattern.     

Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease

BACKGROUND: While patients with interstitial lung disease (ILD) may be particularly susceptible to ventilator-induced lung injury, ventilator strategies have not been studied in this group of patients. PURPOSES: To describe the clinical course and outcome of patients with ILD and acute respiratory failure in relation to ventilatory parameters. METHODS: We retrospectively identified a cohort of ventilated patients with ILD who had been admitted to five ICUs at a single institution. We analyzed demographic data, pulmonary function test results, severity of illness, and the parameters of continuous ventilation for the initial 24 h after admission to the ICU. Primary outcomes were survival to hospital discharge and 1-year survival. Main results: Of 94 patients with ILD, 44 (47%) survived to hospital discharge and 39 (41%) were alive at 1 year. Nonsurvivors were less likely to be postoperative, had higher severity of illness, and were ventilated at higher airway pressures and lower tidal volumes. Step changes in positive end-expiratory pressure (PEEP) of > 10 cm H(2)O were attempted in 20 patients and resulted in an increase in plateau pressure (median difference, + 16 cm H(2)O; interquartile range [IQR], 9 to 24 cm H(2)O) and a decrease in respiratory system compliance (median difference, - 0.28 mL/kg/cm H(2)O; IQR, - 0.43 to - 0.13 mL/kg/cm H(2)O). The Cox proportional hazards model revealed that high PEEP (hazard ratio, 4.72; 95% confidence interval [CI], 2.06 to 11.15), acute physiology and chronic health evaluation (APACHE) III score predicted mortality (hazard ratio 1.33; 95% CI, 1.18 to 1.50), age (hazard ratio, 1.03; 95% CI, 1 to 1.05), and low Pao(2)/fraction of inspired oxygen ratio (hazard ratio, 0.96; 95% CI, 0.92 to 0.99) to be independent determinants of survival. CONCLUSION: Both severity of illness and high PEEP settings are associated with the decreased survival of patients with ILD who are receiving mechanical ventilation.     

Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge

OBJECTIVES: To follow-up on the changes in lung function and lung radiographic pictures of severe acute respiratory syndrome (SARS) patients discharged from Xiaotangshan Hospital in Beijing (by regularly receiving examination), and to analyze retrospectively the treatment strategy in these patients. METHODS: Surviving SARS patients were seen at least twice within 3 months after discharge and underwent SARS-associated coronavirus (SARS-CoV) IgG antibody testing, pulmonary function testing, and chest radiography and/or high-resolution CT (HRCT) examinations at Chinese PLA General Hospital. The treatments received at Xiaotangshan Hospital were analyzed retrospectively and were correlated to later status. RESULTS: Positive SARS-Co virus IgG antibody results were seen in 208 of 258 patients, with 21.3% (55 of 258 patients) still having a pulmonary diffusion abnormality (D(LCO) < 80% of predicted). By comparing the 155 survivors with positive SARS-CoV IgG antibody results and D(LCO) > or = 80% predicted with the 50 patients with negative SARS-CoV IgG results, we found that 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality had endured a much longer course of fever and received larger doses of glucocorticoid, as well as higher ratios of oxygen inhalation and noninvasive ventilation treatment. For these patients, 51 of 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality underwent pulmonary function testing after approximately 1 month. D(LCO) improved in 80.4% of patients (41 of 51 patients). Of the patients with a lung diffusion abnormality, 40 of 51 patients showed lung fibrotic changes in the lung image examination and 22 patients (55%) showed improvement in lung fibrotic changes 1 month later. CONCLUSION: These findings suggest that lung fibrotic changes caused by SARS disease occurred mostly in severely sick patients and may be self-rehabilitated. D(LCO) scores might be more sensitive than HRCT when evaluating lung fibrotic changes.     

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.     

Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value of outpatient testing

BACKGROUND: Cardiac sarcoidosis (CS) causes substantial morbidity and sudden death. Early diagnosis and risk stratification are warranted. METHODS: Ambulatory patients with sarcoidosis were interviewed to determine whether they experienced palpitations, syncope, or presyncope, and were evaluated with ECG, Holter monitoring, and echocardiography (transthoracic echocardiogram [TTE]). Those with symptoms or abnormal results were studied with cardiac MRI (CMRI) or positron emission tomography (PET) scanning. The diagnosis of CS was based on abnormalities detected by these imaging studies. Patients with CS were referred for risk stratification by electrophysiology study (EPS). RESULTS: Among the 62 patients evaluated, the prevalence of CS was 39%. Patients with CS had more cardiac symptoms than those without CS (46% vs 5%, respectively; p < 0.001), and were more likely to have abnormal Holter monitoring findings (50% vs 3%, respectively; p < 0.001) and TTE findings (25% vs 5%, respectively; p = 0.02). The degree of pulmonary impairment did not predict CS. Two of the 17 patients who underwent EPS had abnormal test findings and received implantable cardioverter-defibrillators. No patients died, had ventricular arrhythmias that triggered defibrillator therapy, or had heart failure develop during almost 2 years of follow-up. This diagnostic approach was more sensitive than the established criteria for identifying CS. CONCLUSION: CS is common among patients with sarcoidosis. A structured clinical assessment incorporating advanced cardiac imaging with PET scanning or CMRI is more sensitive than the established criteria for the identification of CS. Sarcoidal lesions seen on CMRI or PET scanning do not predict arrhythmias in ambulatory patients with preserved cardiac function, who appear to be at low risk for short-term mortality.     

Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

BACKGROUND: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity. OBJECTIVE: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay. RESULTS: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients. CONCLUSIONS: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.     

Familial idiopathic pulmonary fibrosis: clinical features and outcome

STUDY OBJECTIVES: Familial idiopathic pulmonary fibrosis (FIPF) has been defined as idiopathic pulmonary fibrosis (IPF) occurring in two or more members of a family. The clinical course of FIPF has not been fully defined. Accordingly, the current study was undertaken to establish clinical, radiologic, and histologic features, and survival in a consecutive series of patients with FIPF. DESIGN: Retrospective analysis of clinical, radiologic, and pathologic data from a consecutive series of patients with FIPF who were seen at Mayo Medical Center. Survival in patients with FIPF was contrasted to that of previously characterized patients with nonfamilial IPF who were evaluated at our institution. SETTING: Tertiary referral medical center. PATIENTS: We screened 47 patients and family members with FIPF from 15 families who were identified between the years 1992 and 2002. We further analyzed the subgroup of FIPF patients that was composed of 27 patients from 15 families in whom the complete clinical course was monitored at our institution. MEASUREMENTS: All patients exhibited clinical features that were compatible with IPF and either compatible high-resolution CT (HRCT) scan findings or histologic evidence of usual interstitial pneumonia. Clinical data, including symptoms, physical findings, HRCT scan findings, lung function test results, biopsy results, and survival were abstracted from the clinical records. RESULTS: Compared to patients with nonfamilial IPF, patients with FIPF did not demonstrate any notable differences in clinical, radiologic, or pathologic features. We observed that the total number of affected members in a family with FIPF was a significant risk factor for earlier mortality (p = 0.0157; hazard ratio, 1.434). Overall, however, patients with FIPF had a statistically similar outcome to those patients with nonfamilial IPF. CONCLUSIONS: Although uncommon, FIPF represents a distinct syndrome, which has clinical features and patient survival rates that are similar to those of nonfamilial IPF.     

Endothelin-1/endothelin-3 ratio: a potential prognostic factor of pulmonary arterial hypertension

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare condition characterized by elevated pulmonary artery pressure leading to right-heart failure and death. Endothelin (ET)-1 has been shown to play a significant pathogenic role in PAH. ET-3 has not yet been investigated in PAH. METHODS: ET-1 and ET-3 plasma concentrations were measured in 33 PAH patients prior to any specific PAH therapy and in 9 control subjects. In PAH patients, hemodynamic parameters measured by right-heart catheterization, 6-min walk distance (6MWD), New York Heart Association (NYHA) functional class, and time until lung transplantation or death were recorded. RESULTS: In patients with PAH, levels of ET-1 were increased while those of ET-3 were decreased, as compared to control subjects (p < 0.005 for both comparisons). ET-1/ET-3 ratio varied little in control subjects, while it increased threefold in PAH patients (p < 0.0001). ET-1 correlated positively with right atrial pressure (RAP), indexed total pulmonary resistance, and negatively with cardiac index and venous saturation of oxygen (Svo(2)). ET-3 correlated positively with 6MWD. ET-1/ET-3 ratio correlated positively with RAP, negatively with Svo(2) and 6MWD, and was also associated with NYHA functional class. ET-1/ET-3 ratio was associated with prognosis in this sample of PAH patients treated with specific therapies. CONCLUSIONS: PAH is characterized by elevated ET-1 and ET-1/ET-3 ratio and decreased ET-3 plasma concentrations. All of them correlate with hemodynamic and clinical markers of disease severity. ET-1/ET-3 ratio might be a novel prognostic factor in PAH. These preliminary data should be validated in a large prospective multicenter cohort of PAH patients.