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Original Research: IDIOPATHIC PULMONARY FIBROSIS |

Baseline BAL Neutrophilia Predicts Early Mortality in Idiopathic Pulmonary Fibrosis* FREE TO VIEW

Brent W. Kinder, MD; Kevin K. Brown, MD, FCCP; Marvin I. Schwarz, MD, FCCP; Joachim H. Ix, MD, MAS; Alma Kervitsky; Talmadge E. King, Jr, MD, FCCP
Author and Funding Information

*From the Department of Medicine (Dr. Kinder), University of Cincinnati College of Medicine, Cincinnati, OH; the Department of Medicine (Drs. Brown, Schwarz, and Kervitsky), National Jewish Medical and Research Center, Denver, CO; the Department of Medicine (Dr. Ix), University of California San Diego, San Diego, CA; and the Department of Medicine (Dr. King), University of California San Francisco School of Medicine, San Francisco, CA.

Correspondence to: Talmadge E. King, Jr, MD, Chair, Department of Medicine, UCSF, 505 Parnassus Ave, M-994, San Francisco, CA 94143; e-mail: tking@medicine.ucsf.edu



Chest. 2008;133(1):226-232. doi:10.1378/chest.07-1948
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Published online

Background: The prognostic value of BAL fluid cell count differential in patients with idiopathic pulmonary fibrosis (IPF) is unknown. We hypothesized that baseline BAL fluid cell count differential (ie, elevated levels of neutrophils and eosinophils, or reduced levels of lymphocytes) would predict higher mortality among persons with IPF.

Methods: We evaluated the association of BAL fluid cell count differential and mortality among 156 persons with surgical lung biopsy-proven IPF who underwent bronchoscopy with BAL and cell count differential measurements at presentation. Vital status was obtained among all participants. Cox regression analysis evaluated the association of BAL fluid cell count differential and mortality.

Results: After controlling for known clinical predictors of mortality, we found that each doubling of baseline BAL fluid neutrophil percentage was associated with a 30% increased risk of mortality (adjusted hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.01 to 1.62; adjusted p = 0.04) in the first year after presentation. We observed no association with BAL fluid lymphocyte percentage and mortality (adjusted HR per doubling, 0.99; 95% CI, 0.76 to 1.29; p = 0.93) or eosinophil percentage and mortality (adjusted HR per doubling, 0.99; 95% CI, 0.69 to 1.40; p = 0.95).

Conclusions: Increased BAL fluid neutrophil percentage is an independent predictor of early mortality among persons with IPF. Alternatively, BAL fluid lymphocyte and eosinophil percentages were not associated with mortality. The clinical utility of BAL at the time of diagnosis of IPF should be reconsidered.

Figures in this Article

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) that is characterized by a poor prognosis and no proven effective treatment.14 It is histologically characterized by the usual interstitial pneumonia (UIP) pattern. The 5-year survival rate is between 20% and 40%.57 To date, the tools available to predict prognosis have been imprecise1,3,811 and have complicated clinical decision making regarding the use of potentially toxic therapies and the timing of referral for lung transplantation.

BAL fluid cellular constituents are used to characterize the inflammatory cellular population in the lungs of patients with IPF. Studies performed before the American Thoracic Society (ATS)/European Respiratory Society reclassification of the idiopathic interstitial pneumonias4 demonstrated that higher BAL fluid neutrophilia and/or eosinophilia predicted a subsequent deterioration in pulmonary function test result parameters, whereas BAL fluid lymphocytosis was associated with a more cellular biopsy, less honeycombing seen on radiographs, and improved responsiveness to immunosuppressive therapy.1216 Since the ATS/European Respiratory Society reclassification of the idiopathic interstitial pneumonias, it has been suggested17that misclassification (in particular, the inclusion of patients with idiopathic nonspecific interstitial pneumonia among the cases of IPF) may have accounted for these findings. Subsequent studies1820 evaluating the association of BAL fluid cellular constituents and mortality have yielded conflicting results about the prognostic value of BAL, and were limited by the size of the study cohort and the duration of follow-up. Thus, the clinical relevance of the enumeration of cellular constituents in BAL fluid as predictors of mortality in patients with IPF remains unknown.

In the present study, we evaluated the association of BAL fluid cellular constituents with mortality among a prospective cohort of persons with IPF in whom the presence of a UIP pattern was confirmed on surgical lung biopsy specimens. We hypothesized that the BAL fluid cell count differential (ie, elevated levels of neutrophils and eosinophils, or reduced levels of lymphocytes) at the time of the diagnosis of IPF would predict mortality in a large cohort of persons with IPF.

Study Subjects

The study cohort consisted of 156 patients with IPF who were prospectively enrolled into a Specialized Center of Research Study at the National Jewish Medical and Research Center between 1982 and 1996. The diagnosis of IPF was made based on established clinical and histologic criteria, as described previously.10 The inclusion and exclusion criteria have been previously reported.10 At the initial visit, all participants underwent clinical, radiographic, and physiologic assessments before undergoing lung biopsy. Subjects were designated as current smokers, former smokers, and never-smokers.10 Analysis of the cellular constituents of BAL fluid was performed in 33 healthy volunteers for comparison with the patients with IPF21 (Table 1 ). All subjects were evaluated as outpatients, and none had clinical evidence of concurrent infection.

Informed consent was obtained from each subject, and the Institutional Human Subject Review Committee approved the protocol. A portion of these study participants have been participants in previously reported studies.1,10,21

BAL

BAL was performed in all participants either awake in an outpatient setting within 3 weeks preceding open-lung biopsy or through an endotracheal tube with the participant under anesthesia just prior to the lung biopsy. BAL fluid was analyzed by standard methods, as previously described.21

Physiologic Evaluation

The physiologic assessment included the measurement of thoracic gas volume and total lung capacity, FVC and FEV1, the volume-pressure relationship of the lungs, the single-breath diffusing capacity of the lung for carbon monoxide (Dlco), and arterial blood gas levels, as previously described.10,22

Pathologic Assessment

All participants underwent open thoracotomy or video-assisted thoracoscopic lung biopsy. In each participant, tissue was obtained from at least two sites, the upper and lower lobes of the same lung. Only persons with findings consistent with UIP were included in this study.2,2324

Clinical and Outcome Assessment

A modified ATS questionnaire25 was used to collect demographic and medical information. Vital status was obtained in all participants through July 31, 2006, by linking patient identifiers with the National Death Index. Participants were censored if they (1) were still alive on July 31, 2006, (2) had received a lung transplant, or (3) died. Survival time was calculated as the time from surgical lung biopsy to censoring.

Treatment Protocol

At study entry, most patients had never received treatment directed at IPF (n = 95; 61% of patients). Twenty-one patients (13%) were not receiving treatment at the time of lung biopsy but had previously received short courses of therapy with corticosteroids or other immunosuppressant agents > 30 d prior to undergoing the lung biopsy; 40 patients (26%) had been treated with corticosteroids or immunosuppressants within 30 d of the biopsy. None of the patients had received significant doses of corticosteroids (defined as a total of 2,700 mg of prednisone in any 90-d period) before diagnosis and entry into the study.

Statistical Analysis

As age-specific, gender-specific, and race-specific clinically established cut points for BAL fluid percentages have not been determined among persons with IPF, we categorized participants into three equal groups for descriptive purposes. Differences in baseline demographic and clinical characteristics were compared across neutrophil tertile groups with the use of analysis of variance or the Kruskal-Wallis test for continuous variables, and the χ2 test or Fisher exact test for categoric variables, as appropriate.

We used Cox regression for the primary analysis to evaluate the associations of BAL fluid neutrophil percentage with mortality. To evaluate the proportional hazards assumptions, we used visual inspection of log-minus-log plots and plots of Schoenfeld residuals vs survival time. Both visual inspection and formal hypothesis testing demonstrated that there was a violation of the assumption of proportional hazards with the BAL fluid neutrophil percentage as the predictor (p = 0.03). We took account of this violation by estimating relative hazards by the number of years since enrollment (censoring participants with events in earlier years). Additionally, continuous trends in the log-relative hazards were evaluated by using time-dependent covariates in a companion analysis.26 Exploratory analysis demonstrated a linear relationship between increasing neutrophil percentage and the risk of mortality. Neutrophil percentage was right-skewed. Therefore, to maximize statistical power, we also log-transformed each predictor variable, and evaluated the association of the log-transformed continuous predictors and mortality. Results are reported as “per doubling” of each predictor. We report the results for the first year of follow-up as this was the interval with the most dramatic relationship between BAL fluid neutrophil percentage and mortality.

Covariates for adjustment were selected a priori, either because they represented important demographic variables (ie, age, gender, and race), and/or because prior reports indicated an association with mortality in patients with IPF (ie, age, smoking status, baseline FVC, Dlco, and alveolar-arterial oxygen pressure difference (P[A-a]O2) composite physiologic index3,1011). Before inclusion, Pearson correlation coefficients between continuous covariates were evaluated to avoid collinearity. None had correlation coefficients of > 0.60. We evaluated for multiplicative interactions on the basis of smoking status, which was selected as a candidate effect modifier a priori on the basis of prior research.,3,8

Two-tailed p values of < 0.05 were considered to be statistically significant. Analyses were performed using a statistical software package (Stata statistical software, version 9; Stata Corp; College Station, TX).

Subject Characteristics

The IPF study cohort included 156 subjects (mean age, 63 years; 66% were men; and 88% were white) [Table 1]. Sixty-seven percent of the cohort were either current or former smokers. At the time of the initial visit, the median duration of illness was 24 months. There were 139 participants censored due to death during the study period (89%). In 10 patients, censoring occurred at the time of transplantation. Six patients (4%) were administratively censored because they were alive at the time of analysis, and one patient was lost to follow-up. There were 617 person-years of follow-up among the 156 study participants. The median follow-up time was 2.5 years (interquartile range [IQR], 1.0 to 5.7 years). The median survival time for all subjects was 20.7 months (95% confidence interval [CI], 4.8 to 124.3) from the time of lung biopsy.

BAL Findings

The differential cell counts (median percentage) found in the IPF cohort showed the following (Table 1): macrophages, 77% (IQR, 58 to 87%); neutrophils, 6% (IQR, 3 to 13%); eosinophils, 2% (IQR, 1 to 6%); lymphocytes, 8% (IQR, 5 to 17%). Sixty-seven percent of the cohort had a neutrophil level of > 3%, a threshold previously demonstrated to be abnormal in BAL fluid samples from healthy control subjects.27

Demographic, Physiology, and Gas Exchange Findings

Exploratory analyses revealed that BAL fluid neutrophil percentage was a predictor of mortality (see next section); thus, the baseline characteristics are shown in relation to BAL fluid neutrophil tertiles (Table 2 ). The highest tertile was composed of patients with baseline neutrophil values of > 11%; the middle tertile was composed of those with neutrophil values between 3% and 10%; and the lowest tertile was composed of those with neutrophil values of ≤ 3%. Compared to persons with BAL fluid neutrophil percentage among the lowest tertile, those with higher BAL fluid neutrophil percentages were younger; had lower values for FVC percent predicted, FEV1 percent predicted, and Dlco percent predicted; and higher P(A-a)O2. Smoking status did not differ across neutrophil groups (Table 2).

Survival Analysis

Figure 1 shows the survival curves among patients with neutrophilia (ie, > 3% neutrophils) and those without neutrophilia (ie, ≤ 3% neutrophils) in BAL fluid samples (overall log-rank p value, 0.18). There were no statistically significant associations between mortality and eosinophilia or lymphocytosis in BAL fluid samples.

The survival analysis demonstrated a linear relationship between increasing neutrophil percentage and the risk of mortality. When the neutrophil percentage was considered as a continuous predictor variable, each doubling in the neutrophil percentage was associated with a nearly 30% increased risk of death or transplantation in adjusted analysis (adjusted hazard ratio [HR], 1.28; 95% CI, 1.01 to 1.62; adjusted p = 0.04) [Table 3 ]. However, this association differed significantly during the period of follow-up (p = 0.03), such that for each subsequent year the hazards for death was associated with a doubling of neutrophil percentage decreased by 6%. There was no evidence for effect modification in this relationship based on smoking status (for interaction, p = 0.33) or whether patients had received treatment (for interaction, p = 0.38). When we substituted a composite physiologic index11 (a strong surrogate for disease extent seen on CT scan) for individual pulmonary function parameters (ie, FVC and Dlco), there was no change in the association between BAL fluid neutrophil percentage and early mortality (HR, 1.27; p = 0.04). We observed no association between either the BAL fluid lymphocyte percentage (adjusted HR per doubling, 0.99; 95% CI, 0.76 to 1.29; p = 0.93) or eosinophil percentage (adjusted HR per doubling, 0.99; 95% CI, 0.69 to 1.40; p = 0.95) and the risk of death or transplantation.

During the first year of follow-up, the event rate (ie, the number of deaths or transplants per number of person-years) was 7.03 among persons in the lowest tertile, 12.61 among those in the middle tertile, and 16.67 among those in the highest tertile (for trend, p = 0.07). As shown in Figure 2 , survival was best among persons in the lowest tertile (ie, those individuals with neutrophil counts within the normal range among healthy volunteers [≤ 3%]), particularly during the first 2 years (p = 0.02 [log-rank]). The median survival time for patients in the lowest tertile was 3.7 years; for those in the second tertile, 2.3 years; and for those in the highest tertile, 1.9 years.

This study examined the association of BAL fluid cellular constituents with survival in a large, well-characterized cohort of IPF patients with long-term and comprehensive follow-up. The data demonstrate that, among persons with IPF, BAL fluid neutrophil percentage obtained at the time of initial diagnosis is an independent predictor of time to death or transplant. The impact was most dramatic in the first year of follow-up and attenuated with time. This association remained essentially unaltered after statistical adjustment for previously established clinical predictors of mortality such as age, smoking status, lung function, and gas exchange. There was no association between mortality and BAL fluid lymphocyte and eosinophil percentages.

There have been conflicting results in previous studies13,1819,28 evaluating the relationship between BAL fluid cellularity and outcome. Prior studies12,1819 were limited by inadequate power, lack of clinically meaningful end points, heterogeneous methodology, and the inclusion of patients with histologic patterns other than UIP (eg, IPF) such as nonspecific interstitial pneumonia.

In our prior study12 of 22 newly diagnosed IPF patients, BAL fluid neutrophil contents did not correlate with the degree of clinical impairment (quantitated by a composite clinical-radiologic-physiologic score based on dyspnea, radiographic abnormalities, and physiologic impairment). However, in the current much larger study, BAL fluid neutrophilia positively correlated with the clinical-radiologic-physiologic score (data not shown). The explanation for these discrepant findings most likely has to do with differences in power and the inclusion of patients with histologic patterns other than UIP in the earlier study. In addition, the earlier study did not find any difference in clinical outcomes after 1 year of follow-up, except for an improved survival time in those patients with lymphocytosis. In the current study, we found that an increased level of lymphocytosis seen in BAL fluid does not predict improved survival.

A study by Veeraraghavan and colleagues18of 35 patients with IPF and at least 1 year of follow-up did not find a statistically significant association between BAL fluid neutrophil counts and survival. Tabuena et al,19 in a study of 81 IPF patients, found that BAL fluid neutrophil and lymphocyte counts predicted mortality in current smokers but not among never-smokers or former smokers in an adjusted analysis. We examined, but did not find, a significant interaction with smoking on the association of BAL fluid neutrophil percentage and mortality. However, it should be noted that the method for BAL fluid collection used by Tabuena et al19 differed from ours and that their patients had an abnormally low neutrophil percentage (overall median level, 1.5%) compared with other populations of IPF patients.1214 Last, given the effect size of BAL fluid neutrophilia that we observed in our study, the absence of an association in the cohort of Tabuena et al19 may have been due to limitations in the power of the study.

Several limitations should be considered when interpreting our results. First, the length of time necessary to acquire sufficient power may have resulted in influences by secular trends in the management of disease. However, it is unlikely that these trends affected the associations reported here, as there was no substantial progress made in the management of patients with IPF during the period of the study. Second, there is the potential for residual confounding by unmeasured but important variables. We attempted to mitigate this possibility by collecting and analyzing all baseline clinical predictors that have been shown to have an influence on mortality. Unfortunately, high-resolution CT (HRCT) scans were not available in the early years of this study; therefore, they were not included in the present analysis. Interestingly, in a recent study29 showing that BAL fluid neutrophilia predicted early mortality in patients with scleroderma and ILD, adjustment for the extent of disease on HRCT scans or Dlco measurements did not attenuate this effect. Similarly, in our present study, the impact of BAL fluid neutrophilia on mortality in IPF patients was not attenuated by adjustment for Dlco or a composite physiologic index (ie, reliable surrogates for disease extent in other ILDs,11,30). This suggests the possibility that BAL fluid neutrophilia is measuring a separate phenomenon and is not just a surrogate for disease severity or extent, as conventionally determined. The relationship between HRCT findings, particularly the extent of the change in honeycombing, and BAL fluid neutrophil percentage in IPF patients is an important question that will require evaluation in future studies.

Sustained neutrophil accumulation in the alveolar space and neutrophil-mediated injury to the alveolar wall are believed to play a role in interstitial fibrosis and abnormal lung repair. Indeed, BAL fluid neutrophilia has been identified as a common finding in IPF patients. We demonstrate that BAL fluid neutrophil percentage at the time of diagnosis of IPF is an independent predictor of time to death or transplantation. Although it cannot be investigated directly in the context of our data, we hypothesize that BAL fluid neutrophilia may occur early in disease given the increased percentage of neutrophils in younger IPF patients and those with a shorter disease duration. Alternatively, BAL fluid neutrophilia may identify a subset of patients with disease that is more “active” or at a period of acceleration. It is also possible that BAL fluid neutrophilia has identified patients during an accelerated phase of tissue damage that may predispose them to an acute exacerbation. Recent reports3132 of high BAL fluid neutrophil percentage in IPF patients during acute exacerbations lend support for this possibility.

Current practice and consensus guidelines24 do not recommend performing BAL with the determination of cellular constituents in BAL fluid at the time of the diagnosis of IPF. The independent nature of the association between BAL fluid neutrophilia and mortality after adjusting for demographic and physiologic predictors suggests that it is potentially measuring a distinct but important biological process and thus may have a complementary role in determining prognosis. When effective therapies for IPF are discovered, the indication for BAL with cellular analysis may become clearer.

Abbreviations: ATS = American Thoracic Society; CI = confidence interval; Dlco = diffusing capacity of the lung for carbon monoxide; HR = hazard ratio; HRCT = high-resolution CT; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; IQR = interquartile range; P(A-a)O2 = alveolar-arterial oxygen pressure difference; UIP = usual interstitial pneumonia

This research was supported by a National Institutes of Health T32 training grant, a Clinical Research Loan Repayment Grant, and Specialized Center of Research (SCOR) grants No. HL-27353 and HL-67671 from the National Heart, Lung, and Blood Institute.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Table Graphic Jump Location
Table 1. Demographic and BAL Cellular Data for Healthy Volunteers and Patients With IPF*
* 

Values are given as the median (range), unless otherwise indicated. Data are taken from McCormack et al.21

 

Age at the time of surgical lung biopsy.

Table Graphic Jump Location
Table 2. Baseline Characteristics and BAL Cellular Profile by Neutrophil Percentage Tertile*
* 

Values are given as the mean ± SD, No. (%), or median (IQR), unless otherwise indicated.

 

p Values are for comparison among the three subgroups, using χ2 analysis, Fisher exact test, or analysis of variance, where appropriate.

 

Data not normally distributed (Kruskal-Wallis test).

Figure Jump LinkFigure 1. The Kaplan-Meier survival curve for patients with IPF with BAL fluid neutrophilia (ie, > 3% neutrophils) and those without neutrophilia (ie, ≤ 3% neutrophils) [p = 0.18 (log-rank test); subjects at risk at year 1, 115; subjects at risk at year 2, 86; subjects at risk at year 3, 66; subjects at risk at year 5, 45; subjects at risk at year 10, 19]. Neuts = neutrophils.Grahic Jump Location
Table Graphic Jump Location
Table 3. Association of BAL White Cell Percentage With Death or Transplant During the First Year of Follow-up
* 

Adjusted for age, gender, race, smoking status, baseline FVC, Dlco, and P(A-a)O2.

Figure Jump LinkFigure 2. The Kaplan-Meier survival curve of patients with IPF based on neutrophil percentage by tertile over the first 4 years of follow-up. In tertile I, n = 53; in tertile II, n = 53; in tertile III, n = 51 (p = 0.02 [log-rank test]; subjects at risk at year 1, 115; subjects at risk at year 2, 86; subjects at risk at year 3, 66; subjects at risk at year 4, 55).Grahic Jump Location

The authors are grateful to Eric Vittinghoff for his help with the statistical analysis; to Thomas V. Colby, James A. Waldron, Jr, Andrew Flint, Carlyne Cool, and Rubin M. Tuder, for their pathological reviews; to Reuben M. Cherniack, Leslie C. Watters, Thaddeus L. Dunn, Anthony Shen, Rebecca L. Mortenson, John Wade, and Eugene Sullivan for their role in enrolling patients; to S. Arlene Niccoli, and Martin Wallace for their expert technical assistance in the laboratory; and to the referring physicians. The authors give special thanks to the patients for allowing the investigators to participate in their care. We would like to remember and express our appreciation to the late William (Whitey) Thurlbeck, Mary Wilcox, and Trudy McDermott for their contributions to this study.

King, TE, Jr, Schwarz, MI, Brown, K, et al (2001) Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality.Am J Respir Crit Care Med164,1025-1032. [PubMed]
 
Bjoraker, JA, Ryu, JH, Edwin, MK, et al Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med1998;157,199-203. [PubMed]
 
Flaherty, KR, Mumford, JA, Murray, S, et al Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia.Am J Respir Crit Care Med2003;168,543-548. [PubMed] [CrossRef]
 
American Thoracic Society European Respiratory Society. American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias.Am J Respir Crit Care Med2002;165,277-304. [PubMed]
 
Raghu, G, Brown, KK, Bradford, WZ, et al A placebo-controlled trial of interferon γ-1b in patients with idiopathic pulmonary fibrosis.N Engl J Med2004;350,125-133. [PubMed]
 
Demedts, M, Behr, J, Buhl, R, et al High-dose acetylcysteine in idiopathic pulmonary fibrosis.N Engl J Med2005;353,2229-2242. [PubMed]
 
Nicholson, AG, Colby, TV, du Bois, RM, et al The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis.Am J Respir Crit Care Med2000;162,2213-2217. [PubMed]
 
Collard, HR, King, TE, Jr, Bartelson, BB, et al Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med2003;168,538-542. [PubMed]
 
Flaherty, KR, Andrei, A-C, Murray, S, et al Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test.Am J Respir Crit Care Med2006;174,803-809. [PubMed]
 
King, TE, Jr, Tooze, JA, Schwarz, MI, et al Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model.Am J Respir Crit Care Med2001;164,1171-1181. [PubMed]
 
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Figures

Figure Jump LinkFigure 1. The Kaplan-Meier survival curve for patients with IPF with BAL fluid neutrophilia (ie, > 3% neutrophils) and those without neutrophilia (ie, ≤ 3% neutrophils) [p = 0.18 (log-rank test); subjects at risk at year 1, 115; subjects at risk at year 2, 86; subjects at risk at year 3, 66; subjects at risk at year 5, 45; subjects at risk at year 10, 19]. Neuts = neutrophils.Grahic Jump Location
Figure Jump LinkFigure 2. The Kaplan-Meier survival curve of patients with IPF based on neutrophil percentage by tertile over the first 4 years of follow-up. In tertile I, n = 53; in tertile II, n = 53; in tertile III, n = 51 (p = 0.02 [log-rank test]; subjects at risk at year 1, 115; subjects at risk at year 2, 86; subjects at risk at year 3, 66; subjects at risk at year 4, 55).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Demographic and BAL Cellular Data for Healthy Volunteers and Patients With IPF*
* 

Values are given as the median (range), unless otherwise indicated. Data are taken from McCormack et al.21

 

Age at the time of surgical lung biopsy.

Table Graphic Jump Location
Table 2. Baseline Characteristics and BAL Cellular Profile by Neutrophil Percentage Tertile*
* 

Values are given as the mean ± SD, No. (%), or median (IQR), unless otherwise indicated.

 

p Values are for comparison among the three subgroups, using χ2 analysis, Fisher exact test, or analysis of variance, where appropriate.

 

Data not normally distributed (Kruskal-Wallis test).

Table Graphic Jump Location
Table 3. Association of BAL White Cell Percentage With Death or Transplant During the First Year of Follow-up
* 

Adjusted for age, gender, race, smoking status, baseline FVC, Dlco, and P(A-a)O2.

References

King, TE, Jr, Schwarz, MI, Brown, K, et al (2001) Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality.Am J Respir Crit Care Med164,1025-1032. [PubMed]
 
Bjoraker, JA, Ryu, JH, Edwin, MK, et al Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med1998;157,199-203. [PubMed]
 
Flaherty, KR, Mumford, JA, Murray, S, et al Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia.Am J Respir Crit Care Med2003;168,543-548. [PubMed] [CrossRef]
 
American Thoracic Society European Respiratory Society. American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias.Am J Respir Crit Care Med2002;165,277-304. [PubMed]
 
Raghu, G, Brown, KK, Bradford, WZ, et al A placebo-controlled trial of interferon γ-1b in patients with idiopathic pulmonary fibrosis.N Engl J Med2004;350,125-133. [PubMed]
 
Demedts, M, Behr, J, Buhl, R, et al High-dose acetylcysteine in idiopathic pulmonary fibrosis.N Engl J Med2005;353,2229-2242. [PubMed]
 
Nicholson, AG, Colby, TV, du Bois, RM, et al The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis.Am J Respir Crit Care Med2000;162,2213-2217. [PubMed]
 
Collard, HR, King, TE, Jr, Bartelson, BB, et al Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med2003;168,538-542. [PubMed]
 
Flaherty, KR, Andrei, A-C, Murray, S, et al Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test.Am J Respir Crit Care Med2006;174,803-809. [PubMed]
 
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