Composite Physiologic Index Research Articles

Pulmonary vascular resistance predicts early mortality in patients with diffuse fibrotic lung disease and suspected pulmonary hypertension

Background:Pulmonary hypertension (PH) is associated with a poor prognosis in diffuse lung disease (DLD). A study was undertaken to compare the prognostic significance of invasive and non-invasive parameters in patients...

Idiopathic Pulmonary Fibrosis

The pathogenic importance of smoking status in idiopathic pulmonary fibrosis (IPF) is uncertain. In theory, increased oxidative stress in current and former smokers might promote disease progression. However, better survival has been reported for current smokers with IPF, although this might reflect less severe disease at presentation (a "healthy smoker effect"). To determine whether smoking status is associated with survival differences in IPF. A total of 249 patients with IPF were studied (current smokers, n = 20; former smokers, n = 166; never-smokers, n = 63). Survival was evaluated against smoking status, using proportional hazards analysis, adjusting for sex, age, disease severity (extent of the disease on high-resolution computed tomography, composite physiologic index [CPI], percentage predicted diffusing capacity for carbon monoxide in separate models), and the degree of honeycombing. Current smokers had milder disease than did former smokers, with lower CPI scores (P < 0.0001), less extensive disease on high-resolution computed tomography (P < 0.005), and higher unadjusted survival (hazard ratio = 0.44; 95% confidence interval = 0.24, 0.80; P = 0.007). However, survival did not differ between current and former smokers (P = 0.39) after adjustment for CPI levels. By contrast, the increase in survival seen in nonsmokers than in former smokers (hazard ratio = 0.51; 95% confidence interval = 0.41, 0.83; P = 0.008) was amplified (P < 0.0005) by adjustment for CPI levels. In IPF, survival and severity-adjusted survival are higher in nonsmokers than in former smokers or the combined group of former and current smokers. By contrast, a better outcome in current smokers, compared with former smokers, reflects less severe disease at presentation and may represent a healthy smoker effect.

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.

Quantification of emphysema: a composite physiologic index derived from CT estimation of disease extent

The combination of functional indices best reflecting the extent of emphysema is not known. High-resolution computed tomography (HRCT) studies of 106 patients with emphysema [men=71; median age=61 (range=26-86 years)] were reviewed and the extent of emphysema was quantified: (a) visually (emphysema(vis)) and (b) by automated estimation (emphysema(auto)). Functional-morphologic relationships were compared for the two scoring systems, and a composite physiologic index (CPI) (providing the best fit of functional indices against emphysema extent) was derived. Emphysema(vis) and emphysema(auto) were strongly correlated (r=0.90; p<0.0005), but the extent of emphysema(vis) was consistently greater (p<0.00005). Emphysema(vis) correlated most strongly with indices of gas transfer [percent predicted single-breath carbon monoxide diffusing capacity (Dl(co)) and alveolar volume (K(co)); r=-0.70, both p<0.0005]. The combination of physiologic indices most representative of emphysema extent on CT (using visual or automated methods) consisted of K(co) and forced expiratory volume in 1 s (FEV(1)) levels. The equation explanatory power was higher for visual scoring [emphysema(vis)=96.8-(0.67 x % predicted K(co))-(0.41 x % predicted FEV(1)); equation r(2)=0.57] than automated estimation (equation r(2)=0.48). Weighted combinations of K(co) and FEV(1) levels provide a CPI best reflecting morphologic emphysema extent. CPI has the potential to refine the stratification of patients in epidemiological and therapeutic studies.

Increased serum vascular endothelial growth factor levels in microscopic poly angiitis with pulmonary involvement

Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that affects small vessels, resulting in a wide spectrum of organ involvement including the lungs. However, there are little serological markers that predict its prognosis or severity of pulmonary involvement. Vascular endothelial growth factor (VEGF) is an angiogenic mediator, which has been reported to be elevated in systemic vasculitis. In this study, we measured serum VEGF levels in 22 MPA patients with pulmonary involvement. We also investigated VEGF expression in pulmonary cells using flow cytometry analysis. We found that serum VEGF levels in MPA patients were significantly higher than those in respiratory or urinary tract infection. The serum VEGF levels decreased in parallel with the improvement of MPA symptoms. The serum VEGF levels in MPA patients who died within 5 years were significantly higher than those who survived more than 5 years. The sensitivity of VEGF levels to distinguish MPA patient with poor prognosis from those with good prognosis was 90.9%, and specificity was 81.8% (cutoff value = 802.5 pg/ml). The serum VEGF levels showed significant positive correlation with the composite physiological index, which indicates the severity of pulmonary lesion. In flow cytometry analysis, CD11b positive bronchoalveolar lavage fluid cells expressed VEGF. Immunohistochemically, alveolar macrophages, tissue infiltrating inflammatory cells and alveolar epithelial cells stained positive for VEGF. Measurement of serum VEGF levels in MPA might become one of the markers for prognosis and the severity of pulmonary involvement in MPA. VEGF might contribute to the development of pulmonary lesion of MPA.

Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection

Objective Pulmonary fibrosis is associated with an increased risk of lung cancer and outcome of surgical resection in this setting is unknown. Methods We studied 22 patients (24 operations) with pulmonary fibrosis and non-small cell lung cancer treated between 1991 and 2000 (study group) and compared outcome with 951 other patients (964 operations) treated for non-small cell lung cancer over the same period (control patients). Results The two groups did not differ significantly in age (68 vs 65 years), smoking history (86% vs 95% smokers), forced expiratory volume in 1 second (2.5 L/min vs 2.3 L/min) or forced vital capacity (3.2 L vs 3.7 L), but patients with pulmonary fibrosis were more likely to be male (72% vs 58%, P < .05). The operative mortality was higher in patients with pulmonary fibrosis than in control patients (17% vs 3.1%, P < .01) and there was a higher procedure-specific mortality in pulmonary fibrosis for pneumonectomy (33% vs 5.1%, P < .01) and lobectomy (12% vs 2.6%, P < .01). Patients with pulmonary fibrosis had a higher incidence of postoperative lung injury, (21% vs 3.7%, P < .01) and a longer mean hospital stay (17 vs 9 days, P < .05). In patients with pulmonary fibrosis, the actuarial 3-year survival was 54%. There were 11 deaths in the study group, 4 postoperatively (all acute respiratory distress syndrome) and 7 late deaths (metastatic disease, n = 2; progressive pulmonary fibrosis, n = 5). Median follow-up (to death or last review) was 13 months (range, 0-120 months). Five patients developed postoperative acute respiratory distress syndrome and in 4 of these patients this proved to be fatal. Postoperative acute respiratory distress syndrome was associated with lower preoperative total lung carbon monoxide diffusion capacity (median, 58% vs 70%, P = .03) and lower preoperative carbon monoxide diffusion capacity corrected for alveolar volume (median, 48% vs 58%, P = .05) and a higher preoperative composite physiological index (median, 44 vs 33, P = .008). None of the preoperative lung function parameters or operative finding were predictors of late death. Conclusion Patients with pulmonary fibrosis undergoing pulmonary resection for non-small cell lung cancer have increased postoperative morbidity and mortality, but an important subgroup has a good long-term outcome. Postoperative acute respiratory distress syndrome is associated with low preoperative gas transfer and a high composite physiological index. Resection of non-small cell lung cancer is appropriate in pulmonary fibrosis, provided that the level of functional impairment is carefully factored into patient selection.

Worsening of Felty's syndrome with methotrexate.

This study aimed to investigate whether the combination of fibrosis and emphysema has a greater effect than the sum of its parts on functional indices and outcome in idiopathic pulmonary fibrosis (IPF), using visual and computer-based (CALIPER) computed tomography (CT) analysis. Consecutive patients (n=272) with a multidisciplinary IPF diagnosis had the extent of interstitial lung disease (ILD) scored visually and by CALIPER. Visually scored emphysema was subcategorised as isolated or mixed with fibrotic lung. The CT scores were evaluated against functional indices forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide (<i>D</i>_LCO), transfer coefficient of the lung for carbon monoxide (<i>K</i>_CO), composite physiologic index (CPI)) and mortality. The presence and extent of emphysema had no impact on survival. Results were maintained following correction for age, gender, smoking status and baseline severity using <i>D</i>_LCO, and combined visual emphysema and ILD extent. Visual emphysema quantitation indicated that relative preservation of lung volumes (FVC) resulted from tractionally dilated airways within fibrotic lung, ventilating areas of admixed emphysema (p&lt;0.0001), with no independent effect on FVC from isolated emphysema. Conversely, only isolated emphysema (p&lt;0.0001) reduced gas transfer (<i>D</i>_LCO). There is no prognostic impact of emphysema in IPF, beyond that explained by the additive extents of both fibrosis and emphysema. With respect to the location of pulmonary fibrosis, emphysema distribution determines the functional effects of emphysema.