Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a better prognosis, on average, than idiopathic pulmonary fibrosis (IPF). We compare survival time and pulmonary function trajectory in patients with HP and IPF by radiologic phenotype. METHODS: HP (n = 117) was diagnosed if surgical/transbronchial lung biopsy, BAL, and exposure history results suggested this diagnosis. IPF (n = 152) was clinically and histopathologically diagnosed. All participants had a baseline high-resolution CT (HRCT) scan and FVC % predicted. Three thoracic radiologists documented radiologic features. Survival time is from HRCT scan to death or lung transplant. Cox proportional hazards models identify variables associated with survival time. Linear mixed models compare post-HRCT scan FVC % predicted trajectories. RESULTS: Subjects were grouped by clinical diagnosis and three mutually exclusive radiologic phenotypes: honeycomb present, non-honeycomb fibrosis (traction bronchiectasis and reticulation) present, and nonfibrotic. Nonfibrotic HP had the longest event-free median survival (> 14.73 years) and improving FVC % predicted (1.92%; 95% CI, 0.49-3.35; P = .009). HP with non-honeycomb fibrosis had longer survival than IPF (> 7.95 vs 5.20 years), and both groups experienced a significant decline in FVC % predicted. Subjects with HP and IPF with honeycombing had poor survival (2.76 and 2.81 years, respectively) and significant decline in FVC % predicted. CONCLUSIONS: Three prognostically distinct, radiologically defined phenotypes are identified among patients with HP. The importance of pursuing a specific diagnosis (eg, HP vs IPF) among patients with non-honeycomb fibrosis is highlighted. When radiologic honeycombing is present, invasive diagnostic testing directed at determining the diagnosis may be of limited value given a uniformly poor prognosis.

Development and validation of a radiological diagnosis model for hypersensitivity pneumonitis.

High-resolution computed tomography (HRCT) may be useful for diagnosing hypersensitivity pneumonitis. Here, we develop and validate a radiological diagnosis model and model-based points score.Patients with interstitial lung disease seen at the University of Michigan Health System (derivation cohort) or enrolling in the Lung Tissue Research Consortium (validation cohort) were included. A thin-section, inspiratory HRCT scan was required. Thoracic radiologists documented radiological features.The derivation cohort comprised 356 subjects (33.9% hypersensitivity pneumonitis) and the validation cohort comprised 424 subjects (15.5% hypersensitivity pneumonitis). An age-, sex- and smoking status-adjusted logistic regression model identified extent of mosaic attenuation or air trapping greater than that of reticulation ("MA-AT>Reticulation"; OR 6.20, 95% CI 3.53-10.90; p<0.0001) and diffuse axial disease distribution (OR 2.33, 95% CI 1.31-4.16; p=0.004) as hypersensitivity pneumonitis predictors (area under the receiver operating characteristic curve 0.814). A model-based score >2 (1 point for axial distribution, 2 points for "MA-AT>Reticulation") has specificity 90% and positive predictive value (PPV) 74% in the derivation cohort and specificity 96% and PPV 44% in the validation cohort. Similar model performance is seen with population restriction to those reporting no exposure (score >2: specificity 91%).When radiological mosaic attenuation or air trapping are more extensive than reticulation and disease has diffuse axial distribution, hypersensitivity pneumonitis specificity is high and false diagnosis risk low (<10%), but PPV is diminished in a low-prevalence setting.

Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease of unknown etiology. Inter-society consensus guidelines on IPF diagnosis and management outline radiologic patterns including definite usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. We evaluate these diagnostic categories as prognostic markers among patients with IPF. METHODS: Included subjects had biopsy-proven UIP, a multidisciplinary team diagnosis of IPF, and a baseline high-resolution computed tomography (HRCT). Thoracic radiologists assigned the radiologic pattern and documented the presence and extent of specific radiologic findings. The outcome of interest was lung transplant-free survival. RESULTS: IPF patients with a possible UIP pattern on HRCT had significantly longer Kaplan-Meier event-free survival compared to those with definite UIP pattern (5.21 and 3.57 years, respectively, p = 0.002). In a multivariable Cox proportional hazards model adjusted for baseline age, gender, %-predicted FVC, and %-predicted DLCO via the GAP Stage, extent of fibrosis (via the traction bronchiectasis score) and ever-smoker status, possible UIP pattern on HRCT (versus definite UIP) was associated with reduced hazard of death or lung transplant (HR = 0.42, CI 95% 0.23-0.78, p = 0.006). CONCLUSIONS: Radiologic diagnosis categories outlined by inter-society consensus guidelines is a widely-reported and potentially useful prognostic marker in IPF patients, with possible UIP pattern on HRCT associated with a favorable prognosis compared to definite UIP pattern, after adjusting for relevant covariates.

Smoking-related idiopathic interstitial pneumonia.

Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.

Reference absolute and indexed values for left and right ventricular volume, function and mass from cardiac computed tomography.

INTRODUCTION: Left ventricular (LV) and right ventricular (RV) volumetric and functional parameters are important biomarkers for morbidity and mortality in patients with heart failure. PURPOSE: To retrospectively determine reference mean values of LV and RV volume, function and mass normalised by age, gender and body surface area (BSA) from retrospectively electrocardiographically gated 64-slice cardiac computed tomography (CCT) by using automated analysis software in healthy adults. MATERIALS AND METHODS: The study was approved by the institutional review board with a waiver of informed consent. Seventy-four healthy subjects (49% female, mean age 49.6 ± 11) free of hypertension and hypercholesterolaemia with a normal CCT formed the study population. Analyses of LV and RV volume (end-diastolic, end-systolic and stroke volumes), function (ejection fraction), LV mass and inter-rater reproducibility were performed with commercially available analysis software capable of automated contour detection. General linear model analysis was performed to assess statistical significance by age group after adjustment for gender and BSA. Bland-Altman analysis assessed the inter-rater agreement. RESULTS: The reference range for LV and RV volume, function, and LV mass was normalised to age, gender and BSA. Statistically significant differences were noted between genders in both LV mass and RV volume (P-value < 0.0001). Age, in concert with gender, was associated with significant differences in RV end-diastolic volume and LV ejection fraction (P-values 0.027 and 0.03). Bland-Altman analysis showed acceptable limits of agreement (±1.5% for ejection fraction) without systematic error. CONCLUSION: LV and RV volume, function and mass normalised to age, gender and BSA can be reported from CCT datasets, providing additional information important for patient management.

Older HIV-infected patients on antiretroviral therapy have B-cell expansion and attenuated CD4 cell increases with immune activation reduction.

BACKGROUND: The contribution of immune activation to accelerated HIV-disease progression in older individuals has not been delineated. METHODS: Prospective multicenter cohort of older (≥45 years) and younger (18-30 years) HIV-infected adults initiating 192 weeks of antiretroviral therapy (ART). Longitudinal models of CD4 cell restoration examined associations with age-group, thymic volume, immune activation, and viral load. RESULTS: Forty-five older and 45 younger adults (median age 50 and 26 years, respectively) were studied. Older patients had fewer naive CD4 cells (P<0.001) and higher HLA-DR/CD38 expression on CD4 (P=0.05) and CD8 cells (P=0.07) than younger patients at any time on ART. The rate of naive and total CD4 cell increase was similar between age groups, but older patients had a faster mean rate of B-cell increase (by +0.7 cells/week; P=0.01), to higher counts than healthy controls after 192 weeks (P=0.003). Naive CD4 increases from baseline were associated with immune activation reductions (as declines from baseline of %CD8 cells expressing HLA-DR/CD38; P<0.0001), but these increases were attenuated in older patients, or in those with small thymuses. A 15% reduction in activation was associated with naive gains of 29.9 and 6.2 cells/µl in younger, versus older patients, or with gains of 25.7, 23.4, and 2.1 cells/µl in patients with the largest, intermediate, and smallest thymuses, respectively (P<0.01 for interactions between activation reduction and age-group or thymic volume). CONCLUSION: Older patients had significant B-cell expansion, higher levels of immune activation markers, and significantly attenuated naive CD4 cell gains associated with activation reduction.

Thoracic CT findings in Birt-Hogg-Dube syndrome.

OBJECTIVE: Birt-Hogg-Dubé syndrome manifests in the thorax as lung cysts. The purpose of this article is to describe the CT characteristics of cysts in patients with Birt-Hogg-Dubé syndrome and to note other thoracic findings. MATERIALS AND METHODS: The thoracic CT examinations of 17 patients with Birt-Hogg-Dubé syndrome were reviewed retrospectively for the presence, anatomic distribution (upper lung predominant, lower lung predominant, or diffuse), extent (size, number), and morphology (shape, wall thickness) of cysts. Any additional thoracic findings were also noted. RESULTS: The study population consisted of 13 women (76%) and four men (24%) with a mean age of 50.2 ±15.2 years. Two patients (12%) had normal findings on CT. Fifteen patients had cystic lung disease, all of whom had more than one cyst. Most patients had bilateral (13/15, 87%) and lower lung-predominant cysts (13/15, 87%). The cysts varied in size from 0.2 to 7.8 cm. The largest cysts were located in the lower lobes of 14 of 15 patients (93%). Of the nine patients with large cysts, most had at least one multiseptated cyst (7/9, 78%). Five of 15 patients (33%) had more than 20 cysts. Cyst shape varied among the 15 patients and also within individual patients (10/15, 67%) ranging from round to oval, lentiform, and multiseptated. Cysts showed no central or peripheral predominance. CONCLUSION: Discrete thin-walled cysts in patients with Birt-Hogg-Dubé syndrome are more numerous and larger in the lower lobes and vary in size and shape. Large lung cysts are frequently multiseptated. These features may aid in differentiating Birt-Hogg-Dubé syndrome from other more common cystic lung diseases.

Optimal anatomic coverage for CT in staging lung cancer: lessons from PET-CT correlation.

OBJECTIVE: To determine the optimal anatomic coverage at CT that would provide the most accurate staging for patients with non-small cell lung cancer. METHODS: We reviewed lung cancer staging PET-CT scans and correlated them with staging chest CT scans performed within 50 days of the PET-CT study. There were 113 patients who underwent both studies within our time frame. We reviewed the results of subsequent imaging studies and surgical and biopsy procedures to determine the final stage for each patient. This study was approved by the local institutional review board. RESULTS: In 86 (76%) of 113 patients, staging by PET-CT and by CT from the lung apices through the lung bases was identical. PET-CT upstaged 21 patients (19%) compared with CT findings; in 13 of these patients the PET-CT noted disease that was either outside of the anatomic range of any lung cancer staging CT or was within the area scanned by CT, but was not evident by CT. In the other 8 upstaged patients, extending the anatomic scope of the CT scan to the supraclavicular region (5), adrenal glands (2) or abdomen (1) would have resulted in correct staging. CONCLUSIONS: CT scanning from the supraclavicular region through the caudal adrenal glands improves the accuracy of CT staging of lung cancer compared with scanning from the lung apices through the lung bases. Anatomic coverage beyond the adrenal glands has a low yield for improved staging, at the cost of requiring administration of oral contrast to all patients. SUMMARY: To determine the optimal anatomic coverage at CT that would provide the most accurate staging for patients with non-small cell lung cancer, we reviewed lung cancer staging PET-CT scans and correlated them with staging chest CT scans performed within 50 days of the PET-CT study. CT scanning from the supraclavicular region through the caudal adrenal glands improves the accuracy of CT staging of lung cancer compared with scanning from the lung apices through the lung bases. Anatomic coverage beyond the adrenal glands has a low yield for improved staging, at the cost of requiring administration of oral contrast to all patients undergoing lung cancer staging.

TLR9 differentiates rapidly from slowly progressing forms of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is characterized by diffuse alveolar damage and severe fibrosis, resulting in a steady worsening of lung function and gas exchange. Because idiopathic pulmonary fibrosis is a generally progressive disorder with highly heterogeneous disease progression, we classified affected patients as either rapid or slow progressors over the first year of follow-up and then identified differences between the two groups to investigate the mechanism governing rapid progression. Previous work from our laboratory has demonstrated that Toll-like receptor 9 (TLR9), a pathogen recognition receptor that recognizes unmethylated CpG motifs in bacterial and viral DNA, promotes myofibroblast differentiation in lung fibroblasts cultured from biopsies of patients with idiopathic pulmonary fibrosis. Therefore, we hypothesized that TLR9 functions as both a sensor of pathogenic molecules and a profibrotic signal in rapidly progressive idiopathic pulmonary fibrosis. Indeed, TLR9 was present at higher concentrations in surgical lung biopsies from rapidly progressive patients than in tissue from slowly progressing patients. Moreover, fibroblasts from rapid progressors were more responsive to the TLR9 agonist, CpG DNA, than were fibroblasts from slowly progressing patients. Using a humanized severe combined immunodeficient mouse, we then demonstrated increased fibrosis in murine lungs receiving human lung fibroblasts from rapid progressors compared with mice receiving fibroblasts from slowly progressing patients. This fibrosis was exacerbated by intranasal CpG challenges. Furthermore, CpG induced the differentiation of blood monocytes into fibrocytes and the epithelial-to-mesenchymal transition of A549 lung epithelial cells. These data suggest that TLR9 may drive the pathogenesis of rapidly progressive idiopathic pulmonary fibrosis and may serve as a potential indicator for this subset of the disease.

Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonias (IIPs) have similar clinical and radiographic features, but their histopathology, response to therapy, and natural history differ. A surgical lung biopsy is often required to distinguish between these entities. OBJECTIVES: We sought to determine if clinical variables could predict a histopathologic diagnosis of IPF in patients without honeycomb change on high-resolution computed tomography (HRCT). METHODS: Data from 97 patients with biopsy-proven IPF and 38 patients with other IIPs were examined. Logistic regression models were built to identify the clinical variables that predict histopathologic diagnosis of IPF. MEASUREMENTS AND MAIN RESULTS: Increasing age and average total HRCT interstitial score on HRCT scan of the chest may predict a biopsy confirmation of IPF. Sex, pulmonary function, presence of desaturation, or distance walked during a 6-minute walk test did not help discriminate pulmonary fibrosis from other IIPs. CONCLUSIONS: Clinical data may be used to predict a diagnosis of IPF over other IIPs. Validation of these data with a prospective study is needed.

The prognostic value of cardiopulmonary exercise testing in idiopathic pulmonary fibrosis.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, impaired gas exchange, and ultimate mortality. OBJECTIVES: To test the hypothesis that maximal oxygen uptake during cardiopulmonary exercise testing at baseline and with short-term longitudinal measures would predict mortality in patients with idiopathic pulmonary fibrosis. METHODS: Data from 117 patients with IPF and longitudinal cardiopulmonary exercise tests were examined retrospectively. Survival was calculated from the date of the first cardiopulmonary exercise test. MEASUREMENTS AND MAIN RESULTS: Patients with baseline maximal oxygen uptake less than 8.3 ml/kg/min had an increased risk of death (n = 8; hazard ratio, 3.24; 95% confidence interval, 1.10-9.56; P = 0.03) after adjusting for age, gender, smoking status, baseline forced vital capacity, and baseline diffusion capacity for carbon monoxide. We were unable to define a unit change in maximal oxygen uptake that predicted survival in our cohort. CONCLUSIONS: We conclude that a threshold maximal oxygen uptake of 8.3 ml/kg/min during cardiopulmonary exercise testing at baseline adds prognostic information for patients with IPF.

Accuracy of high-resolution CT in the diagnosis of diffuse lung disease: effect of predominance and distribution of findings.

OBJECTIVE: The purpose of this study was to determine whether the predominant findings at high-resolution CT influence the accuracy of diagnosis of diffuse lung disease. MATERIALS AND METHODS: The cases of 100 patients with diffuse lung disease who underwent high-resolution CT and tissue diagnosis were studied. Three thoracic radiologists reviewed high-resolution CT images blindly and independently for patterns of abnormality, listing their three main diagnoses and level of confidence in the first choice. The effect of the findings on accuracy was analyzed. RESULTS: For honeycombing, the accuracy of the main diagnosis was 96.6%, 92.2%, and 92.3% for the three readers, and that of the three main diagnoses was 96.6%, 96.1%, and 92.3%. For cysts, the accuracy of the main diagnosis was 88.9%, 80%, and 81.8% and of the three main diagnoses was 100%, 90%, and 90.9%. For bronchovascular thickening, the accuracy of the main diagnosis was 91.7%, 87.5%, and 90.9% and of the three main diagnoses was 91.7%, 100%, and 90.9%. For ground-glass opacification (GGO), the accuracy of the main diagnosis was 75.5%, 55%, and 44.2% and of the three main diagnoses was 89.8%, 75%, and 65.4%. Only combining honeycombing with GGO improved the accuracy of GGO. Anatomic craniocaudal distribution improved reader accuracy when GGO was predominantly present in the lower part of the lung. Interobserver agreement on the presence of major findings was a mean kappa value of 0.45 for honeycombing, 0.74 for lung cysts, 0.63 for bronchovascular thickening, and 0.56 for GGO. Agreement for the craniocaudal distribution of major findings was a mean kappa value of 0.48 for honeycombing, 0.52 for bronchovascular thickening, and 0.32 for GGO. CONCLUSION: The predominant findings of honeycombing and bronchovascular thickening are associated with more than 90% accuracy in the first-choice diagnosis of diffuse lung disease; the finding of lung cysts has 80-89% accuracy. GGO as a predominant pattern had unreliable accuracy, but the accuracy improved when GGO was combined with either honeycombing or lower-lung distribution.

Smoking-related interstitial lung disease: radiologic-clinical-pathologic correlation.

Cigarette smoking is a recognized risk factor for development of interstitial lung disease (ILD). There is strong evidence supporting a causal role for cigarette smoking in development of respiratory bronchiolitis ILD (RB-ILD), desquamative interstitial pneumonitis (DIP), and pulmonary Langerhans cell histiocytosis (PLCH). In addition, former and current smokers may be at increased risk for developing idiopathic pulmonary fibrosis (IPF). The combination of lower lung fibrosis and upper lung emphysema is being increasingly recognized as a distinct clinical entity in smokers. High-resolution computed tomography is sensitive for detection and characterization of ILD and may allow recognition and classification of the smoking-related ILDs (SR-ILDs) into distinct individual entities. However, the clinical, radiologic, and histologic features overlap among the different SR-ILDs, and mixed patterns of disease frequently coexist in the same patient. The overlap is most significant between RB-ILD and DIP. Macrophage accumulation is bronchiolocentric in RB-ILD, producing centrilobular ground-glass opacity, and more diffuse in DIP, producing widespread ground-glass changes. The coexistence of upper lung nodules and cysts in a smoker allows confident diagnosis of PLCH. Final diagnosis of an SR-ILD and identification of the specific entity can be achieved with certainty only after the pulmonologist, radiologist, and pathologist have reviewed all of the clinical, radiologic, and pathologic data.

Idiopathic interstitial pneumonia: do community and academic physicians agree on diagnosis?

RATIONALE: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. OBJECTIVES: Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. METHODS: Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. MEASUREMENTS AND MAIN RESULTS: Each observer's diagnosis was coded into one of eight categories. A kappa statistic allowing for multiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (kappa = 0.55-0.71) than within community centers (kappa = 0.32-0.44). Clinically significant disagreement was present between academic and community-based physicians (kappa = 0.11-0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. CONCLUSIONS: Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.

Thoracic lymph node enlargement in usual interstitial pneumonitis and nonspecific-interstitial pneumonitis: prevalence, correlation with disease activity and temporal evolution.

PURPOSE: To evaluate the prevalence of thoracic lymph node enlargement (LNE) in usual (UIP) and nonspecific (NSIP) interstitial pneumonitis, change in LNE over time, and if LNE is related to disease activity. METHODS AND MATERIALS: High-resolution CT scans (HRCT) in 20 patients each with UIP and NSIP were retrospectively reviewed. Two HRCT scans were reviewed for each patient, at diagnosis and a mean of 1 +/- 0.7 years later. Two thoracic radiologists independently recorded the location and size of thoracic lymph nodes (LNs) > 10-mm in short-axis diameter, using the American Thoracic Society lymph node mapping scheme. HRCT disease severity was scored for ground glass opacity and fibrosis. The number and size of enlarged LN stations were compared with HRCT scores. RESULTS: LNE was found on 44 HRCT examinations (21 baseline prevalence 52.5%, 23 follow-up, prevalence 57.5%), most common in the low right paratracheal (38%) and subcarinal (36%) regions. There was no significant difference in LN size or number of enlarged LN stations between baseline and follow-up CT. LNE prevalence was not different on baseline CT (P = 0.34) follow-up CT (P = 0.11) between UIP and NSIP patients. The mean size of the largest enlarged LN was 1.36 cm (1 to 2.1 cm) at baseline and 1.43 cm (1 to 1.9 cm) on follow-up CT. Mean CT ground glass and fibrosis scores were 1.98 and 1.6 when LNE was present, and 1.34 and 1.03 when absent (P = 0.008 and 0.003, respectively). The number and maximum size of enlarged LNs did not correlate with CT ground glass or fibrosis scores. Five patients who developed LNE between baseline and follow-up CT examinations had a greater increase in CT fibrosis scores than patients whose LNE status did not change (P = 0.004); CT ground glass scores were not significantly different. There was a trend for UIP patients to progress from absence of LNE to presence of LNE (4/20 patients or 20%). CONCLUSIONS: Intrathoracic LNE is common in both UIP and NSIP, and becomes increasingly prevalent in UIP patients over time. LNE is more prevalent with more severe lung disease. An increase in LNE over time is associated with the progression of fibrosis, and should not raise concern for co-existing infection or malignancy, in the absence of other clinical findings that would suggest this.

Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia.

PURPOSE: To determine which clinical and radiologic findings are independently associated with a pathologic diagnosis of usual interstitial pneumonia (UIP). METHODS: We recently reported, using a prospective, multicenter study of patients suspected of having idiopathic interstitial pneumonia (IIP), that a confident diagnosis of UIP made by experienced radiologists was correct in 95% of cases. In the current article, we further analyzed data from this study. Ninety-one patients were entered into the study. Clinical, physiologic, chest radiographic, and CT features were prospectively recorded, and analyzed using univariate and multivariate logistic regression analysis to compare the patients with a histologic diagnosis of UIP with those who received other pathologic diagnoses. RESULTS: Fifty-four of 91 patients (59%) received a pathologic diagnosis of UIP. The following features recorded at the referring clinical centers were associated with a pathologic diagnosis of UIP on multivariate analysis: lower-lobe honeycombing on high-resolution CT (HRCT) [odds ratio, 11.45], radiographic findings consistent with UIP (odds ratio, 5.73), elevated ratio of FEV(1) to FVC (odds ratio, 4.8), and absence of smoking history (odds ratio, 0.19). On multivariate analysis of specific HRCT features recorded by four experienced chest radiologists, lower-lung honeycombing (odds ratio, 5.36) and upper-lung irregular lines (odds ratio, 6.28) were the only independent predictors of UIP. Using only these two factors, a diagnosis of UIP could be established with a sensitivity of 74%, a specificity of 81%, and a positive predictive value of 85%. CONCLUSION: In patients presenting with a clinical syndrome suggestive of IIP, CT findings of lower-lung honeycombing and upper-lung irregular lines are most closely associated with a pathologic diagnosis of UIP.

Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia.

Exercise-induced hypoxia is an index of the severity of interstitial lung disease. We hypothesized that desaturation during a 6-minute walk test would predict mortality for patients with usual interstitial pneumonia (n = 83) and nonspecific interstitial pneumonia (n = 22). Consecutive patients with biopsy-proven disease performed a 6-minute walk test between January 1996 and December 2001. Desaturation was defined as a fall in oxygen saturation to 88% or less during the 6-minute walk test. Desaturation was common (44 of 83 usual interstitial pneumonia and 8 of 22 nonspecific interstitial pneumonia; chi square, p = 0.39). Patients with usual interstitial pneumonia or nonspecific interstitial pneumonia who desaturated had a significantly higher mortality than patients who did not desaturate (respective log-rank tests, p = 0.0018, p = 0.0089). In patients with usual interstitial pneumonia, the presence of desaturation was associated with an increased hazard of death (hazard ratio, 4.2; 95% confidence interval, 1.40, 12.56; p = 0.01) after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, FVC, and resting saturation. We conclude that knowledge of desaturation during a 6-minute walk test adds prognostic information for patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.

Age-related immune dysfunction in health and in human immunodeficiency virus (HIV) disease: association of age and HIV infection with naive CD8+ cell depletion, reduced expression of CD28 on CD8+ cells, and reduced thymic volumes.

Older age is a strong predictor of accelerated human immunodeficiency virus (HIV) disease progression. We investigated the possible immunologic basis of this interaction by comparing older (>/=45 years) and younger (

Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia.

Idiopathic interstitial pneumonias are a diverse group of lung diseases with varied prognoses. We hypothesized that changes in physiologic and radiographic parameters would predict survival. We retrospectively examined 80 patients with usual interstitial pneumonia and 29 patients with nonspecific interstitial pneumonia. Baseline characteristics were examined together with 6-month change in forced vital capacity, diffusing capacity for carbon monoxide, and ground glass infiltrate and fibrosis on high resolution computed tomography. Patients with usual interstitial pneumonia were more likely to have a statistically significant or marginally significant decline in lung volume, diffusing capacity for carbon monoxide, and an increase in ground glass infiltrates (p < or = 0.08) compared with patients with nonspecific interstitial pneumonia. For patients with usual interstitial pneumonia, change in forced vital capacity was the best physiologic predictor of mortality (p = 0.05). In a multivariate Cox proportional hazards model controlling for histopathologic diagnosis, gender, smoking history, baseline forced vital capacity, and 6-month change in forced vital capacity, a decrease in forced vital capacity remained an independent risk factor for mortality (decrease > 10%; hazard ratio 2.47; 95% confidence interval 1.29, 4.73; p = 0.006). We conclude that a 6-month change in forced vital capacity gives additional prognostic information to baseline features for patients with idiopathic interstitial pneumonia.

Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease.

A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease-associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease-associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease-associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.