Low DLCO Research Articles

Measurement of respiratory function: an update on gas exchange

Gas exchange is the main function of the lungs. Oxygen and carbon dioxide diffuse along their partial pressure gradient across the alveolar-capillary membrane. Lungs have a large reserve for gas exchange. Alveolar ventilation and pulmonary circulation are closely matched to provide efficient gas exchange in the lungs. Hypoxaemia often results from mismatch in ventilation–perfusion. Gas exchange can be impaired in various disease states. Measurement of the diffusing capacity for carbon monoxide (DLCO) provides estimation of the gas exchange function. A low DLCO indicates an impairment of oxygen transfer across the alveolar-capillary membrane. Anaesthesia and surgery adversely affect pulmonary function, many of which adverse effects can be prevented.

Predictors of Fatigue Severity in Early Systemic Sclerosis: A Prospective Longitudinal Study of the GENISOS Cohort

ObjectivesLongitudinal studies examining the baseline predictors of fatigue in SSc have not been reported. Our objectives were to examine the course of fatigue severity over time and to identify baseline clinical, demographic, and psychosocial predictors of sequentially obtained fatigue scores in early SSc. We also examined baseline predictors of change in fatigue severity over time.MethodsWe analyzed 1090 longitudinal Fatigue Severity Scale (FSS) scores belonging to 256 patients who were enrolled in the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS). Predictive significance of baseline variables for sequentially obtained FSS scores was examined with generalized linear mixed models. Predictors of change in FSS over time were examined by adding an interaction term between the baseline variable and time-in-study to the model.ResultsThe patients' mean age was 48.6 years, 47% were Caucasians, and 59% had diffuse cutaneous involvement. The mean disease duration at enrollment was 2.5 years. The FSS was obtained at enrollment and follow-up visits (mean follow-up time = 3.8 years). Average baseline FSS score was 4.7(±0.96). The FSS was relatively stable and did not show a consistent trend for change over time (p = 0.221). In a multivariable model of objective clinical variables, higher Medsger Gastrointestinal (p = 0.006) and Joint (p = 0.024) Severity Indices, and anti-U1-RNP antibodies (p = 0.024) were independent predictors of higher FSS. In the final model, ineffective coping skills captured by higher Illness Behavior Questionnaire scores (p<0.001), higher self-reported pain (p = 0.006), and higher Medsger Gastrointestinal Severity Index (p = 0.009) at enrollment were independent predictors of higher longitudinal FSS scores. Baseline DLco % predicted was the only independent variable that significantly predicted a change in FSS scores over time (p = 0.013), with lower DLco levels predicting an increase in FSS over time.ConclusionsThis study identified potentially modifiable clinical and psychological factors that predict longitudinal fatigue severity in early SSc.

Clinical Characteristics and Survival in Systemic Sclerosis-Related Pulmonary Hypertension Associated With Interstitial Lung Disease

Pulmonary hypertension (PH) complicating systemic sclerosis (SSc)-related interstitial lung disease (ILD) is usually associated with a poor prognosis. However, data are either lacking or scarce on prognostic factors in this condition. The objectives of this study were to compare the survival of patients with ILD-associated PH (PH-ILD) or pulmonary arterial hypertension (PAH) and to determine whether the severity of PH has prognostic value in SSc-associated PH-ILD. Consecutive patients with SSc and PH-ILD (n = 47) or PAH (n = 50) confirmed by right-sided heart catheterization were included in a cross-sectional analysis. PH was classified as mild (mean pulmonary arterial pressure [mPAP] ≤ 35 mm Hg) or moderate to severe (mPAP > 35 mm Hg). As compared with patients with PAH, subjects with PH-ILD were younger, were more frequently men with a history of smoking, had more frequently diffuse SSc, less frequently anticentromere antibodies, and a lower FVC/diffusing capacity of lung for carbon monoxide (DLCO) ratio. They had a worse prognosis than patients with PAH (3-year survival of 47% vs 71%, respectively; P = .07). Patients with mild PH-ILD had similar poor outcomes when compared with those with moderate to severe PH-ILD. Pericardial effusion (hazard ratio [HR], 2.44; P = .04) and lower DLCO (HR, 0.96; P = .01) were the only independent factors predictive of a poor survival in the PH-ILD group. Patients with SSc with PH-ILD had a different phenotype and a worse prognosis than those with SSc and PAH. Lower DLCO and presence of pericardial effusion were predictive of a poor outcome in PH-ILD, whereas mPAP seemed to have no prognostic significance.

Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres

ObjectiveSystemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but...

Impaired carbon monoxide diffusing capacity as a marker of limited systemic sclerosis

Background As impairment of diffusing capacity for carbon monoxide (DLCO) likely reflects underlying pulmonary vasculopathy in limited systemic sclerosis (lSSc), we examined whether DLCO could help to distinguish secondary from idiopathic Raynaud's phenomenon (iRP). Methods We compared pulmonary function test (PFT) results in 145 lSSc patients and 24 age- and sex-matched iRP patients. RP duration at time of PFT was similar in the two groups. Results DLCO values were low (< 80% of predicted) in 106 (73%) of the 145 lSSc patients, and in 69 (71%) of the 97 patients with early lSSc. Interstitial lung disease (ILD) was found in 10% of lSSc patients. DLCO was significantly lower in lSSc than in iRP (72 ± 15% versus 89 ± 9%, p < 0.0001). When evaluated, alveolar capillary membrane conductance (Dm) was markedly lower in lSSc patients without ILD than in iRP patients (45 ± 12% versus 71 ± 2.5%, p = 0.003), although capillary blood volume was not different. DLCO was low in 3 iRP patients (12.5%). The sensitivity and specificity of low DLCO values for early lSSc diagnosis in patients with Raynaud's phenomenon were 71% and 87.5%, respectively. Sensitivity was similar to that of anti-centromere-antibodies (75%) and nailfold capillary abnormalities (81%). A DLCO cutoff of < 70% had a sensitivity and specificity of 41% and 100%, respectively. In multivariable analysis, age and low DLCO were the only independent predictors of death; the hazard ratio for DLCO ≤ 50% was 7.9 (95% CI 2.3–26, p = 0.0007). Conclusion Isolated DLCO impairment is significantly more frequent in patients with lSSc than in patients with idiopathic iRP. DLCO measurement could be a useful diagnostic tool for lSSc.

Associations with digital ulcers in a large cohort of systemic sclerosis: Results from the Canadian Scleroderma Research Group registry

Digital ulcers are a common complication of systemic sclerosis (SSc; scleroderma). Approximately half of SSc patients have had a digital ulcer, but information is lacking on whether digital ulcers are associated with patient demographics and clinical outcomes. We wanted to determine the associations between digital ulcers and other SSc vascular complications and organ involvement. Data from the Canadian Scleroderma Research Group are collected annually on SSc patients, including presence, location, and number of digital ulcers; complications from digital ulcers; internal organ involvement; skin score; and laboratory results. Correlation coefficients, chi-square test, and logistic regression modeling were done to determine the associations of digital ulcers with other factors, including internal organ complications. A total of 938 patients were included; 86% were women, the mean age was 55 years, the mean disease duration was 13.6 years, and 50% had limited cutaneous SSc. Eight percent had a digital ulcer currently and 44% had a digital ulcer ever; 53.1% had digital pitting scars. Digital ulcers were associated with increased modified Rodnan skin score (P = 0.0001), hand and finger skin score (P = 0.0001), Health Assessment Questionnaire score (P = 0.0001) and disease duration (P = 0.001), younger age of SSc onset (P = 0.0001), interstitial lung disease (ILD; P = 0.0001), and topoisomerase I (Scl-70) antibodies (P = 0.0001) in limited and diffuse cutaneous SSc subsets. Digital ulcers were not associated with sex (P = 0.95), smoking (P = 0.9), pulmonary arterial hypertension (PAH; P = 0.35), and scleroderma renal crisis (SRC; P = 0.569). Digital ulcers were further associated with reduced diffusing capacity for carbon monoxide (DLCO; P = 0.0001) and esophageal involvement (P = 0.0001) in diffuse cutaneous SSc only. Digital ulcers are associated with worse disease, including skin and lung involvement, but are not associated with PAH and SRC. However, the low DLCO that is associated with SRC could represent ILD or microvasculopathy.

Characterization of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension From REVEAL: Identifying Systemic Sclerosis as a Unique Phenotype

REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH).All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA).Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P < .0001), and lower diffusing capacity of carbon monoxide (Dlco) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P < .0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P < .0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest Dlco (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH).Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest Dlco, and poorest survival of all CTD-APAH subgroups.ClinicalTrials.gov; No.: NCT00370214; URL: clinicaltrials.gov.

Poor FEV1 or DLco on Pre-Transplant PFT Does Not Compromise Outcomes In Patients Undergoing a Reduced-Intensity Allogeneic Progenitor Cell Transplant.

AbstractAbstract 1322 Background:Pre-transplant work-up prior to an allogeneic stem cell transplant (allo-SCT) generally includes pulmonary functions tests (PFT) with assessment of FEV1 and DLco. It has been previously published that patients with a DLco or FEV1 less than 60% of predicted have higher non-relapse mortality (NRM) when undergoing a myeloablative allo-SCT. However, the PFT criteria for selecting candidates for a reduced intensity (RI) allogeneic transplant allo-SCT remains poorly investigated. We performed a retrospective analysis to assess the impact of low FEV1 or DLco on NRM and overall survival (OS) in patients undergoing a RI allo-SCT. Methods:All patients who underwent a RI allo-SCT for hematological malignancies at MD Anderson Cancer Center from Jan 2000 to April 2009 were included. Using Cox's proportional hazards regression, we compared the rate of NRM and OS between patients who had a pre-transplant FEV1 or DLco > 50% (control group) prior to a RI allo-SCT and those with FEV1 and DLco < 50% (study group). The cumulative incidence of NRM was estimated considering disease progression as a competing risk. Actuarial OS was estimated by the Kaplan-Meier method. Results:Patient characteristics are presented in Table 1. There were no statistically significant differences between the study and control groups except for age and sex. A significantly higher proportion of patients were > 50 years in the control group (65%) compared with the low PFT group (45%, P=0.02) and there were more males in the control group (P=.001). The median FEV1 and DLco in the study group was 55% (28-111) and 47% (33-98) of predicted, respectively. On univariate analysis abnormal PFTs did not impact OS at 30 months (HR 1.1, 95% CI 0.7–1.8, P=0.7) or NRM at 1 year (HR 1.3, (95% CI 0.6–2.7, P=0.4). Active disease at SCT, and a diagnosis of CLL, NHL or HL were associated with significantly worse OS and NRM, whereas age >50 years was only associated with worse OS. Low PFT had no significant impact on OS and NRM when evaluated separately in patients older or younger than 50 years old. Conclusion:Our experience suggests that a low (<50% of predicted) FEV1 or a DLco on pre-transplant evaluation does not adversely impact NRM and OS after RI allo-SCT. These findings need to be validated in a multivariate analysis.Table 1:Patient CharacteristicsLow PFT (N, %)Control (N, %)p–valueNumber of patients33774Follow–up (Median, range) months33 (5–95)28 (1–116)Age, Median, years (range)48 (21–77)55 (20–77)0.06Sex, male12 (36%)497 (64%)0.001Active disease at RI allo-SCT24 (73%)555 (72%)0.9Donor:MRD19 (58%)332 (43%)0.09MUD13 (39%)373 (48%)Other1 (3%)69 (9%)Cell Source:Peripheral blood25 (76%)505(65%)0.2Bone marrow8 (24%)269 (35%)Diagnosis:AML/MDS/ALL/CML15 (48%)337 (43%)0.7CLL/NHL/HL12 (36%)337 (43%)MM/AA/Other5 (15%)100 (13%)Table 2:Cumulative incidence of Non-relapse mortality and ActuarialSurvivalLow PFTs (N=33)Control (N=774)p–value% NRM3 months12 (95% CI 5–30)10 (95% CI 8–13)0.812 months25 (95% CI 13–45)21 (95% CI 18–25)0.4% OS:3 months88 (95% CI 71–95)88 (95% CI 85–90)0.912 months53 (95% CI 34–68)62 (95% CI 58–65)0.3 Disclosures:No relevant conflicts of interest to declare.

Pulmonary outcome in juvenile dermatomyositis: a case-control study

ObjectivesTo compare pulmonary function in patients with juvenile dermatomyositis (JDM) with that of matched controls; and to examine associations between pulmonary function impairment, high-resolution CT (HRCT) abnormalities and other disease...

Pulmonary hypertension after ventriculoatrial shunt implantation

Ventriculoatrial (VA) shunts inserted for the treatment of hydrocephalus are known to be a risk factor for pulmonary hypertension. The aim of this study was to evaluate the incidence of pulmonary hypertension among adult patients with VA shunts. All patients who had received a VA shunt at one of two institutions between 1985 and 2000 were invited for a cardiopulmonary evaluation. The investigation included a thorough history taking, clinical examination, echocardiography, and pulmonary function testing including diffusing capacity of the lung for carbon monoxide (DLCO). Pulmonary hypertension was defined as systolic pulmonary artery pressure>35 mm Hg at rest. The study group consisted of 86 patients, of whom 38 (44%) could be examined. The patients' mean age was 47.1±18.4 years; the median interval between shunt insertion and cardiopulmonary evaluation was 15 years (range 5-20 years). Of the 38 patients, 20 (53%) had Doppler velocity profiles of tricuspid regurgitation that were adequate for the estimation of pulmonary artery systolic pressure. Doppler-defined pulmonary hypertension was observed in 3 patients (8%), 2 of whom underwent right heart catheterization. Chronic thromboembolic pulmonary hypertension was confirmed in both patients, and medical therapy, including anticoagulation, was started. The VA shunt was removed in both cases and replaced with a different type of device. Pulmonary function tests revealed a restrictive pattern in 15% and typical obstructive findings in 9% of patients. In 30% of patients the DLCO was less than 80% of predicted, and blood gas analysis showed hypoxemia in 6% of patients. No significant differences in pulmonary function tests were noted between the patients with and without echocardiographic evidence of pulmonary hypertension. However, patients with pulmonary hypertension had significantly lower DLCO values. The authors detected pulmonary hypertension by using Doppler echocardiography in a significant proportion of patients with VA shunts. It is therefore recommended that practitioners perform regular echocardiography and pulmonary function tests, including single-breath DLCO in these patients to screen for pulmonary hypertension to prevent hazardous late cardiopulmonary complications.

Interstitial Lung Disease in Classic and Skin-Predominant Dermatomyositis

(1) To determine the prevalence of interstitial lung disease (ILD) and isolated low diffusing capacity for carbon monoxide (DLCO) in a large cohort of outpatients with dermatomyositis. (2) To compare the pulmonary abnormalities of patients with classic dermatomyositis and those with skin-predominant dermatomyositis. Retrospective cohort study. University hospital outpatient dermatology referral center. Patients Medical records of 91 outpatients with adult-onset dermatomyositis seen between May 26, 2006, and May 25, 2009, were reviewed. Presence of ILD on thin-slice chest computed tomographic (CT) scans and DLCO. Of the 71 patients with dermatomyositis who had CT or DLCO data, 16 (23%; 95% confidence interval [CI], 13%-33%) had ILD as defined by CT results [corrected]. All patients with ILD had a reduced DLCO, and the ILD prevalence was not different between patients with skin-predominant dermatomyositis (10 of 35 [29% ]) and those with classic dermatomyositis (6 of 36 [17% ]) (P = .27). Eighteen of 71 patients with dermatomyositis (25%; 95% CI, 15%-36%) (7 of 35 [20%] with skin-predominant dermatomyositis; 11 of 36 [31%] with classic dermatomyositis; P = .41) had a low DLCO in the absence of CT findings showing ILD. The prevalence of malignant disease was higher in patients with classic dermatomyositis than in those with skin-predominant dermatomyositis (P = .02), and no patients with skin-predominant dermatomyositis had internal malignant disease. Radiologic ILD and isolated DLCO reductions, which may signify early ILD or pulmonary hypertension, are common in dermatology outpatients with both classic and skin-predominant dermatomyositis. Because DLCO testing is both inexpensive and sensitive for pulmonary disease, it may be appropriate to screen all patients with dermatomyositis with serial DLCO measurements and base further testing on DLCO results.

Patterns of pulmonary dysfunction in asbestos workers: a cross-sectional study.

BackgroundRestrictive patterns of pulmonary function abnormalities associated with asbestos exposure are well described. Studies are less consistent, however, regarding the association of asbestos inhalation with airway dysfunction and obstructive impairment.MethodsWe compared pulmonary function test results between 277 chrysotile exposed workers (22% non-smokers) and 177 unexposed controls (50.3% non-smokers). Information on exposure and smoking were collected using a standardized questionnaire. Standardized spirometric and DCLO Measurement methods were utilized. CXRs were read based on ILO pneumoconiosis guidelines.ResultsAsbestos exposed subjects had significantly reduced FVC, FEV1, FEV1/FVC and DLCO. Restricting the analysis to non-smokers, asbestos workers still had about 3% lower FEV1/FVC ratio than controls, but this difference did not reach statistical significance. Among exposed workers, the presence of radiographic evidence of asbestosis further lowered FVC and DLCO but not FEV1/FVC compared to asbestos exposure without radiographic asbestosis. Additionally, smoking asbestos workers had significantly lower DLCO compared to non-smoking workers.ConclusionAsbestos exposure, especially when radiographic evidence of interstitial fibrosis from asbestosis is present, leads to significant decreases in FVC, FEV1 and the DLCO. However, asbestos exposure alone is not significantly associated with a reduction of the FEV1/FVC. Smoking-asbestos workers had significantly lower DLCO than their non-smoking counterparts. Whether asbestos interacts with smoking additively or synergistically on DLCO needs further investigation. Similarly, further studies are needed to assess the progression and clinical significance of asbestos induced airway dysfunction.

Pulmonary veno-occlusive disease: Recent progress and current challenges

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary arterial hypertension characterised by a progressive obstruction of small pulmonary veins that leads to elevation in pulmonary vascular resistance and right ventricular failure. Despite improved understanding and more efficacious treatment options for PAH overall, the prognosis of PVOD remains dismal. Without therapeutic intervention few patients would be expected to survive more than two years. PVOD may occur in both idiopathic and heritable forms, or develop in association with connective tissue disease, chronic respiratory disease, malignancy or bone marrow transplantation, among other causes. A widespread fibrous intimal proliferation that predominantly involves the pulmonary venules and small veins is the key histopathological hallmark. Surgical lung biopsy is considered the definitive diagnostic test but is associated with significant risk and is not recommended. Distinguishing PVOD from PAH on clinical grounds alone is generally not possible, although PVOD is characterised by a higher male/female ratio and higher tobacco exposure. Instead, non-invasive tests may be helpful and the diagnosis is usually based on an integrated assessment that incorporates high resolution computed tomography (septal lines, ground-glass opacities and lymph node enlargement), pulmonary function testing (lower DLCO), arterial blood gas analysis (lower PaO(2) at rest) and bronchoalveolar lavage (occult alveolar haemorrhage). Treatment of PVOD remains challenging as exposure to pulmonary vasodilators and PAH-specific agents may precipitate acute pulmonary oedema. Nonetheless, a number of successful outcomes describing cautious use of prostanoids, endothelin antagonists and phosphodiesterase type-5 inhibitors have been described. Unfortunately, the long term effects of these agents are variable and lung transplantation remains the treatment of choice.

075 Echocardiographic Determinants of Diffusing Lung Capacity in Patients with Cardiovascular Disease

Alterations of diffusion lung carbon monoxide (DLco) and alveolar-capillary membrane gas conduction (Dm) are associated with poor prognosis in patients with heart failure (HF) or stable coronary artery disease (CAD) even when LV systolic function is preserved. However, the impact of LV function on diffusing lung capacity is poorly understood. Twelve healthy subjects were compared to 19 patients with stable HF and LV systolic dysfunction and to 12 patients with stable CAD and preserved LV systolic function. Diffusing lung capacity was assessed by DLco and Dm, using single breath technique and Roughton-Forster method. Comprehensive transthoracic echocardiography was performed to evaluate LV ejection fraction (EF), Sa velocity, global longitudinal strain (GLS), E and Ea velocities and E/Ea ratio. Demographic and clinical data were similar between the 3 groups. However, HF group were significantly older than control or CAD groups (65±7 vs. 54±12 or 56±7yrs, p<0.01). Compared to control subjects, patients with CAD or HF had lower DLco and Dm (33±6 vs. 25±6 vs. 20.5±6, p<0.01; 55±17 vs. 37±10 vs. 30±11ml.min-1.mmHg-1, p<0.01). In the whole cohort, DLco was correlated with systolic and diastolic parameters (LVEF: r=0.47, p=0.001; GLS: r=0.35, p=0.02; Sa: r=0.49, p=0.0007; E/Ea: r=-0.30, p=0.05; Ea: r=0.51, p=0.0006). Similar results were found with Dm (LVEF: r=0.44, p=0.004; GLS: r=0.33, p=0.03; Sa: r=0.47, p=0.001 and E/Ea: r=-0.36, p=0.02; Ea: r=0.49, p=0.0009). On multivariate analysis, after adjustment for age, sex and BMI, independent predictors of DLco as well as Dm were Ea (r2=0.27, p=0.0006; r2=0.25, p=0.001) and LVEF<50% (r2=0.08, p=0.03; r2=0.07, p=0.03). Reduced diffusing lung capacity is related to both LV diastolic and systolic dysfunctions. Ea-wave velocity is the strongest determinant of this alteration, emphasizing the crucial role of LV relaxation. These findings could explain diffusing lung abnormalities observed in patients with preserved LV systolic function.

T cell activation profiles in different granulomatous interstitial lung diseases – a role for CD8+CD28null cells?

Lymphocytes play a crucial role in lung inflammation. Different interstitial lung diseases may show distinct lymphocyte activation profiles. The aim of this study was to examine the expression of a variety of activation markers on T lymphocyte subsets from blood and bronchoalveolar lavage fluid (BALF) of patients with different granulomatous interstitial lung diseases and healthy controls. Bronchoalveolar lavage cells and blood cells from 23 sarcoidosis patients, seven patients with hypersensitivity pneumonitis and 24 healthy controls were analysed. Lymphocyte activation status was determined by flow cytometry. Lymphocytes were stained with antibodies against CD3, CD4, CD8, CD25, CD28, CD69, very late antigen-1 (VLA)-1, VLA-4 and human leucocyte antigen D-related (HLA-DR). In general, CD28, CD69 and VLA-1 expression on BALF CD4+ lymphocytes and HLA-DR expression on BALF CD8+ lymphocytes was different in patients with hypersensitivity pneumonitis and sarcoidosis patients with parenchymal involvement. This BALF lymphocyte phenotype correlated with carbon monoxide diffusing lung capacity (Dlco) values across interstitial lung diseases (ILD) (r2 = 0.48, P = 0.0002). In sarcoidosis patients, CD8+CD28(null) blood lymphocytes correlated with lower Dlco values (r = -0.66, P = 0.004), chronic BALF lymphocyte activation phenotype (r2 = 0.65, P < 0.0001), radiographic staging (stage I versus stage II and higher, P = 0.006) and with the need for corticosteroid treatment (P = 0.001). Higher expression of CD69, VLA-1 and HLA-DR and lower expression of CD28 on BALF lymphocytes suggests prolonged stimulation and chronic lymphocyte activation in patients with ILD. In sarcoidosis, blood CD8+CD28(null) cells might be a new biomarker for disease severity but needs further investigation.

Respiratory Function in Patients With Stable Anorexia Nervosa

The impact of undernutrition on lung physiology and respiratory muscle performance is still incompletely investigated. The purpose of this study was to assess the functional consequences of malnutrition on the respiratory system in stable patients with anorexia nervosa (AN). Pulmonary function tests, maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax), and the parameters of control of breathing were obtained in 27 patients with AN (mean [+/- SD] age, 24 +/- 7 years; BMI, 16 +/- 1 kg/m(2); duration of disease, 6 +/- 6 years) and in a group of matched healthy subjects. Compared with control subjects, significant reductions in the diffusing capacity of the lung for carbon monoxide (Dlco) and lung diffusion capacity corrected for alveolar ventilation (p < 0.001), which progressively worsened with the duration of disease, were found in the AN group. Only the membrane diffusing capacity was reduced in patients with AN (p < 0.05), while pulmonary capillary blood volume was similar to that of control subjects. Lung density measurements based on CT scan analysis were normal in a subgroup of eight patients with AN with low Dlco. Both Pimax and Pemax were decreased in patients with AN (p < 0.001), but the mild-to-moderate impairment to generate force of the respiratory muscles did not progress with time. In these patients with AN, the parameters of control of breathing were in the normal range and were comparable to those of control subjects. The functional alterations found in patients with AN indicate the presence of the progressive enlargement of peripheral lung units without relevant alveolar septa destruction. In the first 3 years of disease, appreciable weakness of respiratory muscles develops in patients with stable AN without further impairment over time.

Carbon Monoxide Diffusion Capacity: How Low Can You Go for Hematopoietic Cell Transplantation Eligibility?

Current guidelines suggest that patients with a pretransplantation diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 60% are not ideal candidates for hematopoietic cell transplantation (HCT); however, recent studies suggest this criterion may exclude patients who will benefit from the procedure. We conducted a study of all adult patients who underwent autologous or allogeneic HCT between 1990 and 2005, and had a DLCO < 60%, of predicted normal, to examine whether there is a lower limit for the DLCO threshold in the context of respiratory failure and nonrelapse mortality risk (NRM), and whether a comprehensive risk scoring system, such as the Pretransplant Assessment of Mortality (PAM) risk score, can more effectively risk stratify these patients with a very low pretransplantation DLCO. We found that among patients with a DLCO ≤ 60% the risk of respiratory failure or NRM was not significantly different; however, the PAM score effectively risk-stratified these patients for NRM risk. There was a stepwise relationship between PAM score category and NRM risk; the highest PAM score category was associated with a 4.38-fold increase in risk ( P < .001). These findings suggest that the pretransplantation DLCO should not be considered the sole eligibility criteria for allogeneic HCT.

Complications of lung biopsy in patients with idiopathic interstitial pneumonia and risk factors thereof

To investigate the complication rate of lung biopsy in patients with idiopathic interstitial pneumonia (IIP) and the risk factors thereof. The clinical data of 66 IIP patients underwent lung biopsy were analyzed. Of the 66 patients, 21 undergoing surgical lung biopsy (SLB) including open lung biopsy (OLB) (n = 11) and video-assisted thoracic surgery (VATS) (n = 10), and 45 patients undergoing biopsy other than SLB, including transbronchial lung biopsy (TBLB, n = 28) and CT or B mode ultrasonography-guided percutaneous transthoracic needle lung biopsy (n = 17). The general postoperative complication rate was 40.9% (27/66), and the postoperative complication rate was 71.4% (15/21) in the SLB group, significantly higher than that of the non-SLB group (26.7%, 12/45, chi2 = 4.55, P = 0.03). The complications of the SLB group included prolonged air leakage (n = 10, 47.6%), pleural effusion (n = 5, 23.8%), acute pulmonary edema (n = 5, 23.8%), and postoperative pulmonary infection (n = 4, 19.0%), and the complications of the non-SLB group included pneumothorax after percutaneous transthoracic lung needle biopsy or TBLB (n = 12, 26.7%), acute exacerbation (AE) (n = 2, 4.4%), respiratory failure requiring mechanical ventilation for more than 72 h (n = 1, 2.2%), and postoperative pulmonary infection (n = 1, 2.2%). The predicted diffusing capacity of the lings for carbon monoxide (DLCO%) of the SLB group patients with postoperative complications was (46. 83 +/- 17.01)%, significantly higher than that of the SLB group patients without postoperative complication [(75.93 +/- 25.62)%, t = 2.55, P = 0.02]. However, there were not significant differences in the lung function and blood gas indexes among the patients undergoing different procedures of lung biopsy, with and without postoperative complications. Six of the 66 patents died within 90 postoperative days with a mortality of 9.1%, the causes of death of 3 of which were associated with lung biopsy. The IIP patients undergoing SLB suffer from more postoperative complications than those undergoing other lung biopsy procedures with the lower DLCO% as the probable associated factor. AE in the IIP patients can be induced by CT-guided percutaneous transthoracic needle lung biopsy and TBLB, and results in death.

Clinical Predictors and Histologic Appearance of Acute Exacerbations in Chronic Hypersensitivity Pneumonitis

Acute exacerbations (AEs) in idiopathic pulmonary fibrosis (IPF) are critical factors for its clinical course and prognosis. We have seen AEs and poor prognosis consequent to AE in patients with chronic hypersensitivity pneumonitis (HP), as has been seen in patients with IPF. The aim of this study was to evaluate the clinical features of the patients with AE in those with chronic HP. We reviewed 100 consecutive patients with chronic bird fancier lung (BFL) from 1993 to 2006, and analyzed the clinical characteristics, including history, and laboratory and immunologic, imaging, BAL, and histologic findings. AE developed in 14 patients during this observation period (AE group), whereas 86 patients remained stable (non-AE [NAE] group). The 2-year frequency of AE among patients with chronic BFL having usual interstitial pneumonia (UIP)-like lesions seen on surgical lung specimens was 11.5%. Patients with AE were more likely to be smokers (p = 0.003). In pulmonary function test results, the mean total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (Dlco) were lower in patients with AEs (TLC: AE patients, 63.0 +/- 16.8%; NAE patients, 81.6 +/- 20.0%; Dlco: AE patients, 41.9 +/- 19.0%; NAE patients, 60.0 +/- 19.4%). The mean number of lymphocytes in BAL fluid were lower (AE patients, 13.7 +/- 7.5 lymphocytes; NAE patients, 37.2 +/- 29.7 lymphocytes), while the number of neutrophils were greater in AE patients (AE patients, 10.7 +/- 17.6 neutrophils; NAE patients, 3.6 +/- 4.4 neutrophils). Histologic and/or radiologic findings revealed that all AE patients had UIP-like lesions. Diffuse alveolar damage was observed in six cases, whereas organizing pneumonia superimposed on preexistent fibrotic lesions was observed in two cases. The present study showed several predictive factors for AE at the time of diagnosis. Low TLC and Dlco, low lymphocyte levels in BAL fluid, and a UIP-like pattern in histology at the time of diagnosis may be the risk factors for AE.

Prognostic Determinants among Clinical, Thin-Section CT, and Histopathologic Findings for Fibrotic Idiopathic Interstitial Pneumonias: Tertiary Hospital Study

To evaluate the utility of clinical, thin-section computed tomography (CT), and histopathologic findings in predicting the prognosis of patients with usual interstitial pneumonia (UIP) or fibrotic nonspecific interstitial pneumonia (NSIP). The institutional review board approved this retrospective study, with waiver of informed consent. Included were 108 patients (71 men, 37 women; mean age, 61 years +/- 8 [standard deviation]) with UIP (n = 79; 60 men, 19 women; mean age, 63 years +/- 7.4) and fibrotic NSIP (n = 29; 11 men, 18 women; mean age, 57 years +/- 12.9). Patients underwent pulmonary function tests (PFTs), bronchoalveolar lavage (BAL) fluid analysis, and thin-section CT. Two chest radiologists independently assigned scores for the extent of lung abnormalities detected at CT twice at 3-month intervals. The effect of histopathologic diagnoses and clinical and thin-section CT features on survival was evaluated by using Cox regression analyses. The 5-year survival rate (mean follow-up, 45 months) of patients with fibrotic NSIP was 76% in contrast to 46% for patients with UIP (P = .006). With multivariate analysis, a high fibrotic score (the extent of reticulation plus honeycombing) (hazard ratio = 1.200, P = .043) and an initial low diffusing capacity of lung for carbon monoxide (Dlco) level (hazard ratio = 0.973, P = .025) were identified as associated with increased death risk. Patients with UIP or fibrotic NSIP who have a high fibrotic score determined at thin-section CT and a low Dlco level appear to have a high death risk.