Idiopathic Pulmonary Fibrosis Group Research Articles

Cognitive function in idiopathic pulmonary fibrosis.

The purpose of this study was to investigate whether there is evidence that individuals with severe idiopathic pulmonary fibrosis (IPF) have cognitive deficits when compared to individuals with healthy lungs. Participants completed five neuropsychological tests: Trail Making Test (TMT) A and B, Stroop Color Word Test (1, 2, 3), Hopkins Verbal Learning Test, Boston Naming Test, and Grooved Pegboard Test, additionally, the short form-36 and Beck Depression Index. Twelve participants (7 male, mean age 69.3, 9.4 years) comprised the severe IPF group defined by a diffusion capacity for carbon monoxide (DLCO) <30%. Thirty-four patients (22 male, mean age 63.2, 9.6 years) comprised the mild-to-moderate group with a DLCO >30%. Participating spouses (n = 15, 4 male) served as the control group and had a mean age of 66.0, 10.8 years. Controlling for gender and age, the severe group had a significantly longer mean TMT B time (69.4, 135.9 seconds) than the mild group and the control group (86.7 seconds vs 83.2 seconds; p = 0.004 and 0.008 respectively), suggesting inferior performance on tasks requiring speed divided attention. In addition, the severe group had a significantly lower number of correctly identified colors in the Stroop 3 test (22.4 vs 30.6 vs 38.6; p < 0.001), suggesting slower processing speeds when requiring suppression of a familiar response. Participants with severe IPF had worse cognitive function than mild IPF or control subjects. Further research is needed to explain these findings and to develop interventions tailored to address these deficits.

The relationship between idiopathic pulmonary fibrosis and gastroesophageal reflux disease

To study the prevalence and characteristics of gastroesophageal reflux disease (GERD) in patients with idiopathic pulmonary fibrosis (IPF). A total of 48 patients with diffuse parenchymal lung disease (DPLD) including 25 IPF and 23 other DPLD were enrolled from Department of Respiratory Disease in the First Affiliated Hospital of China Medical University. All patients were subjected to 24-hour esophageal pH monitoring. Pulmonary function test and HRCT of lung were performed at the same time. The prevalence of GERD in IPF patients was 64.0%, which was significantly higher than that in other DPLD patients. DeMeester scores were significantly higher in IPF patients than those in non-IPF group [(22.8 ± 21.5) score vs (15.7 ± 14.0) score respectively P < 0.05]. Numbers of reflux longer than 5 minutes [(3.8 ± 4.1) time vs (2.1 ± 2.1) time respectively) and reflux index (1.8 ± 1.7 vs 1.3 ± 1.2) in IPF group were higher than those in non-IPF group, yet without statistical significance. Patients with IPF had significantly higher values of following parameters than those in non-IPF patients including percentage of total reflux time (pH < 4.0) (9.2 ± 5.1)%, percentage of upright reflux time (8.5 ± 5.2)%, percentage of supine reflux time (10.8 ± 10.7)%, numbers of reflux (54.2 ± 22.7) time, numbers of regurgitation longer than 5 minutes (6.3 ± 4.2) time, the longest reflux time (14.5 ± 15.3) min, reflux index 2.5 ± 1.7 and DeMeester scores (34.9 ± 20.3) time (P < 0.05). DeMeester score was positively correlated with gastroesophageal reflux diseases questionnaire (GerdQ) score (r = 0.667, P < 0.01). The prevalence of typical GERD sympotoms in the IPF-GERD patients was higher (heartburn 7/16, regurgitation 6/16) than that in IPF patients without GERD (heartburn 2/9, regurgitation 1/9). Patients with IPF have a high prevalence of GERD, but usually without typical GERD symptoms. In the hospitals 24-hour esophageal pH monitoring not available, GerdQ can be used to identify GERD in IPF patients.

Pulmonary Resection for Lung Cancer in Patients With Idiopathic Interstitial Pneumonia

After pulmonary resection, patients with lung cancer who have idiopathic pulmonary fibrosis (IPF) have been reported to have higher pulmonary morbidity and mortality and poorer outcomes than patients without IPF. However, whether morbidity, mortality, and outcomes differ according to the subtype of idiopathic interstitial pneumonia (IIP) remains unclear. The clinical records of 678 patients with non-small cell lung cancer who underwent pulmonary resection were reviewed retrospectively. A total of 103 patients had IIP and were classified into an IPF group and a non-IPF group in accordance with the 2011 statement. The IPF group comprised 46 patients, and the non-IPF group comprised 57. The 5-year survival rate was significantly higher in the non-IPF group (53.2%) than in the IPF group (22.1%; p= 0.0093). Cause of death was IIP-related respiratory failure in 26.1% (12 of 46) of the patients in the IPF group as compared with 7.0% (4 of 57) of patients in the non-IPF group (p= 0.008). Multivariate Cox analysis indicated that IPF was a significant predictor of long-term survival (hazard ratio 1.910, 95% confidence interval: 1.102 to 3.313; p= 0.021). Idiopathic pulmonary fibrosis is independently associated with poorer overall survival in patients with lung cancer who undergo pulmonary resection. The decision whether to perform surgery in patients who have lung cancer with IIP should therefore take into account the subtype of IIP and the poorer outcomes associated with IPF.

Serum levels of matrix metalloproteinases in patients with idiopathic pulmonary fibrosis and their clinical value

Objective To investigate serum levels of matrix metalloproteinase (MMP)-1, -2 and -9 in patients with idiopathic pulmonary fibrosis (IPF), and to assess their clinical value. Methods 39 clinically confirmed IPF cases and 36 healthy controls were recruited. A sample of 5 ml peripheral blood was collected from each individual and serum levels of MMP-1, -2 and -9 were detected by the enzyme-linked immunosorbent assay.Forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO) were measured in IPF patients. Serum levels of MMP-1, -2 and -9 were compared between the groups. The correlations between serum levels of MMPs and lung function indicators were analyzed. Results The median serum levels of MMP-1, MMP-2 and MMP-9 were higher in the IPF group than in the control group〔906.30 (613.50-1139.23) μg/L vs. 808.38 (596.59-1249.36) μg/L, 9.13 (5.95-11.92) μg/L vs. 7.72 (5.28-10.35) μg/L, 14.56 (8.24-18.96) μg/L vs. 11.38 (8.07-17.14) μg/L, Z=-2.397, -3.564, -4.152, respectively, P=0.017, 0.000, 0.000〕. In patients with IPF, the serum level of MMP-2 was negatively correlated with DLCO% (r=-0.53, P=0.011) and the serum level of MMP-9 had a negative correlation with FVC% (r=-0.49, P=0.020) and DLCO% (r=-0.58, P=0.005). Conclusions Taken together, serum MMP-1 , MMP-2 and MMP-9 levels may help in the clinical diagnosis of IPF. MMP-2 and MMP-9 may be important biomarkers to predict the prognosis of IPF. Key words: Pulmonary fibrosis; Matrix metalloproteinases

Pulmonary hypertension is associated with increased post-lung transplant mortality risk in patients with chronic obstructive pulmonary disease

Pulmonary hypertension associated with lung disease (PHLD) has been shown to be a predictor of disease severity and survival in patients awaiting lung transplantation. Little is known about the relationship of PHLD and survival after lung transplantation or how this may vary by disease. This study evaluated the effect of PHLD on 1-year survival after lung transplantation for patients with the 3 most common indications for transplantation: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and cystic fibrosis (CF). Organ Procurement and Transplantation Network data were obtained for all lung transplant recipients who received an allograft between May 2005 and June 2010. The relationship between PHLD and 1-year survival after lung transplantation for each diagnostic group was examined with Kaplan-Meier estimates and Cox regression. Covariates included in the model were those defined in the current Lung Allocation Score system post-transplant survival model, including age, serum creatinine, percentage predicted forced vital capacity, functional status, and mechanical ventilation use at time of transplant. The estimated relative risk was calculated using Poisson regression with robust error variance and adjustment for covariates. Sample sizes for COPD, IPF, and CF patients were 2,025, 2,304, and 866, respectively. The 1-year post-transplant survival for COPD patients with PHLD was 76.9% vs 86.2% for COPD patients without PHLD (p = 0.001). In multivariate Cox regression analysis COPD patients with PHLD had a 1.74 (95% confidence interval, 1.3-2.3) times higher risk of 1-year post-transplant mortality (p = 0.001). Similar analyses for IPF and CF diagnostic groups showed no significant difference in survival between patients with and without PHLD. COPD patients with PHLD have increased post-transplant 1-year mortality. No significant difference was seen in patients with IPF or CF. Further studies to evaluate the potential mechanisms for this difference between diagnoses are needed.

Interstitial Pneumonia Related to Undifferentiated Connective Tissue Disease: Pathologic Pattern and Prognosis

Undifferentiated connective tissue disease (UCTD) involves conditions characterized by both having symptoms of connective tissue disease (CTD) and autoantibodies but not fulfilling the criteria of a specific CTD. The frequency or prognosis of the usual interstitial pneumonia (UIP) pattern in UCTD is unknown, which may be confused with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the frequency of the UIP pattern in interstitial pneumonia related to UCTD and compare its prognosis with that of IPF and UCTD-nonspecific interstitial pneumonia (UCTD-NSIP). The medical records of 788 patients presumptively diagnosed with idiopathic interstitial pneumonia at Asan Medical Center from January 2005 to December 2012 were retrospectively reviewed. UCTD was diagnosed according to the criteria by Corte and colleagues, and the prognoses were compared between UCTD-UIP and UCTD-NSIP and between UCTD-UIP and IPF. Among 105 patients with UCTD (13.3% of total subjects), 44 had a UIP pattern (by surgical lung biopsy: 24; by high-resolution CT scan: 20), 29 had a nonspecific interstitial pneumonia pattern (by surgical lung biopsy), and nine had an organizing pneumonia pattern (by biopsy). The overall survival of the UCTD-UIP group was shorter than that of the UCTD-NSIP group (P = .021) but significantly better than that of the IPF group (P = .042). A UIP pattern, which seems to be frequent in UCTD, showed a poorer prognosis than that of UCTD-NSIP. However, the prognosis of UCTD-UIP was significantly better than that of IPF, highlighting the importance of searching for underlying UCTD in suspected IPF cases.

Diagnostic Values For Club Cell Secretory Protein (CC16) in Serum of Patients of Combined Pulmonary Fibrosis and Emphysema

Combined pulmonary fibrosis and emphysema (CPFE) is an under-recognized syndrome for which the diagnostic use of serum biomarkers is an attractive possibility. We hypothesized that CC16 and/or TGF-β1 or combinations with other biomarkers are useful for diagnosing CPFE. Patients with respiratory symptoms and a smoking history, with or without chronic obstructive pulmonary disease, were divided into the following three groups according to findings of high-resolution computed tomography of the chest: controls without either emphysema or fibrosis, patients with emphysema alone, and patients compatible with the diagnosis of CPFE. Serum concentrations of CC16, TGF-β1, SP-D, and KL-6 were measured in patients whose condition was stable for at least 3 months. To investigate changes in biomarkers of lung fibrosis in patients with a life-long smoking history, additional measurements were performed on the patients with idiopathic pulmonary fibrosis (IPF) of smoking history. The mean age of the first three groups was 68.0 years, whereas that of the IPF group was 71.8 years, and the groups contained 36, 115, 27, and 10 individuals, respectively. The serum concentration of CC16 in the four groups was 5.67 ± 0.42, 5.66 ± 0.35, 9.38 ± 1.04 and 22.15 ± 4.64 ng/ml, respectively, indicating that those patients with lung fibrosis had a significantly higher concentration. The combined use of CC16, SP-D, and KL-6 provided supportive diagnosis in conjunction with radiological imaging in diagnosis of CPFE. We conclude that a combination of biomarkers including CC16 could provide useful information to screen and predict the possible diagnosis of CPFE.

The expressions and meanings of BMP-7 and TGF-β in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia

To investigate the expressions of cytokines in idiopathic pulmonary fibrosis (IPF) and in idiopathic nonspecific interstitial pneumonia (INSIP); To discuss expressions and meanings of bone morphogenetic protein 7 (BMP-7) and transforming growth factor beta (TGF-β) in IPF and IPF. Selected 47 cases of idiopathic interstitial pneumonia (IIP), which were diagnosed by clinical-radiologic-pathologic (CRP), and classified into two groups which were group IPF (25 IPF) and group INSIP (22 INSIP, including 6 cellular pattern and 16 fibrosing pattern). The normal lung tissues were collected as the control group: The fresh tissues were made to detect more than 114 kinds of cytokines' expressions via Oligo GEArray gene microarray technology. Made a tissue microarray which applied EnVision immunohistochemistry technology to detect the expressions of BMP-7 and TGF-β in both kinds of IIPs. The two groups of patients were followed-up visited around 5 to 8 years and the survival curves were evaluated by Kaplan-Meier method. According to gene microarray results, these two groups were up-expression in TGF family,IL family and TNF family. Most of BMP members were down-expression, in comparison with the control group, except BMP-5,BMP-8B and BMP-15. As the tissue microarray results demonstrated, compared with normal lung tissues,BMP-7 expressed decreasingly in IPF and INSIP groups (t1 = 27.618, P < 0.001; t2 = -12.404, P < 0.001). The expression of IPF were lower than INSIP (t = 5.387, P < 0.05); In INSIP group, patients of cellular pattern expressed BMP-7 more than fibrosing pattern's (t = -5.341, P < 0.001). There were dramatically increasing expressions of TGF-β in IPF and INSIP, when compared with the control group (t1 = 23.393, P < 0.001; t2 = -13.445, P < 0.001) and it presented negative correlation with BMP-7(group IPF: r = -0.771, P < 0.001; group INSIP: r = -0.729, P < 0.001). (3) Clinical follow-up data showed, the stability(improvement), deterioration and death rates of the group IPF and the group INSIP were, respectively, 0(0%), 2 (8%), 23 (92%) and 15 (68.1%), 3 (13.6%), 4 (18.2%). The results were statistically significant (all P < 0.05). The median survival time of the part with higher BMP-7 expression and the part with relatively lower BMP-7 expression, in the group IPF, were 110.8 and 66.4 months (t = -2.686, P < 0.05); In the group INSIP, were 146.4 and 74.9 months (t = -3.037, P < 0.05). Cellular cytokines presented different expression profiles in IPF and INSIP patients. Differently with highly activated TGF-β, BMP-7 was inhibited in IIP patients, which would remind the degree of fibrosis and prognosis of IIP. BMP-7 would be expected to be a novel target for IIP pathogenesis and prognostic research.

Survival and quality of life in rheumatoid arthritis–associated interstitial lung disease after lung transplantation

Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have increased mortality with limited treatment options. We set out to examine post-transplant survival in RA-ILD patients compared with patients with idiopathic pulmonary fibrosis (IPF) and scleroderma-associated ILD (SSc-ILD). We also describe post-transplant quality of life (QoL) outcomes in RA-ILD. A retrospective review was performed on lung transplantation (1989 to 2011) among patients with RA-ILD, IPF (group-matched for age and transplant year) and SSc-ILD. Cumulative survival after transplantation was estimated by the Kaplan-Meier method and compared between groups using the log-rank test. The 36-item Medical Outcomes Survey Short Form (SF-36) and the St. George's Respiratory Questionnaire (SGRQ) scores, before and after lung transplantation, were analyzed. Overall, 10 patients with RA-ILD, 53 with IPF and 17 with SSc-ILD underwent lung transplantation with ages (mean ± SD) of 59.4 ± 5.6, 61.0 ± 4.0 and 45.4 ± 12.7 years, respectively. Cumulative survival rates at 1-year post-transplant for the RA-ILD, IPF and SSc-ILD groups were 67%, 69% and 82%, respectively, and there was no significant difference among groups in age- and gender-adjusted analyses. Among the RA-ILD patients, mean SF-36 physical component summary scores improved from 22.4 ± 8.1 to 32.2 ± 12.9 (p = 0.1), SF-36 mental component summary scores improved from 44.7 ± 15.3 to 54.9 ± 4.8 (p = 0.19) and SGRQ total scores improved from 70.4 ± 16.1 to 36.0 ± 18.5 (p = 0.03). After lung transplantation, RA-ILD and IPF patients have similar survival rates. Further, in RA-ILD patients, lung transplantation appears to result in a significant improvement in QoL with regard to respiratory symptoms. These data suggest that lung transplantation should be considered in patients with end-stage RA-ILD.

Ventilatory efficiency and exercise capacity during exercise in patients with idiopathic pulmonary fibrosis

Objective To explore the characteristics of ventilatory efficiency and exercise capacity during cardiopulmonary exercise testing in patients with idiopathic pulmonary fibrosis (IPF). Methods Pulmonary function test, arterial blood gas analysis and cardiopulmonary exercise testing were performed in 28 IPF patients (IPF group) from April 2012 to April 2013 and 28 healthy volunteers (control group). And the relevant parameters were measured and compared. Results No significant differences existed in age [(57.8±9.8) vs. (59.2±5.5) years], gender or body mass index (BMI) [(23.8±2.7) vs. (25.0±2.8)kg/m2,P>0.05]. The parameters of pulmonary function test, such as forced vital capacity % predicted (74.8±14.6 vs.101.8±10.8), forced expiratory volume in 1 second % predicted (73.8±14.6 vs.97.0±10.1), maximum voluntary ventilation % predicted (77.5±14.9 vs. 95.4±24.5), total lung capacity % predicted (75.6±12.4 vs. 99.8±5.4), residual volume % predicted (80.7±15.4 vs.95.8±11.3), diffusing capacity of lung for carbon monoxide % predicted (66.2±13.7 vs. 103.2±17.3) in the IPF group, were significantly lower than those of the control group (P<0.01). The parameters of arterial blood gas analysis, such as PaO2 [(72.7±7.3) vs. (92.6±3.8)mmHg] and SaO2 (94.3±2.1 vs. 98.3±0.7), were lower than those of the control group (P<0.01). Thus P(A-a)O2 in the IPF group was higher than that in the control group (33.3±5.7 vs. 17.8±1.9, P<0.01). These results strongly suggested that IPF group had restrictive ventilatory dysfunction and impaired gas exchange .The IPF patients had higher VE/VCO2-slope (37.4±5.3 vs. 25.7±2.5, P<0.01) and lowest VE/VCO2 (39.2±6.7 vs. 30.6±2.7, P<0.01) than the controls; VE/VCO2 and VD/VT during every period were significantly higher in the IPF group than those in the control group(P<0.01); during peak exercise, peakLoad%pred (70.4±29.9 vs. 104.8±29.7, P<0.01) and peakVO2%pred (68.7±29.8 vs. 98.7±36.4, P=0.001) were significantly lower in the IPF group than those in the control group. In the IPF group, VE/VCO2@AT, VE/VCO2-slope and lowest VE/VCO2 had a negative correlation with DLCO%pred (r=-0.589, P<0.01; r=-0.481, P<0.05; r=-0.527, P<0.05). In the IPF group, VE/VCO2@AT, VE/VCO2-slope and lowest VE/VCO2 had a negative correlation with peakVO2%pred (r=-0.548, P<0.05; r=-0.539, P<0.05; r=-0.564, P<0.05). So the exercise tolerance and ventilation efficiency of the IPF group decreased significantly. Conclusion Cardiopulmonary exercise testing reveals that the ventilation efficiency of IPF patients decreases significantly so as to seriously affect their exercise tolerance . Key words: Pulmonary fibrosis; Exercise test; Respiratory function tests; Blood gas analysis

Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes

TERT and MUC5B polymorphisms have been associated consistently with idiopathic pulmonary fibrosis (IPF) in recent genomewide genetic studies. However, it remains unclear how both loci contribute to the susceptibility to different entities of sporadic interstitial lung disease (ILD). We sought to test the associations of the 2 polymorphisms with IPF and non-IPF ILD entities in a white population. Associations between 2 polymorphisms in TERT (rs2736100) and MUC5B (rs35705950) and IPF or non-IPF sporadic ILD were tested using 227 patients with ILD and 689 control subjects. Genotypic data were also correlated with pulmonary functions measured in patients with ILD. As a result, rs2736100 and rs35705950 were associated significantly and independently with ILD as a single phenotype (Odds ratio [OR],1.29; 95% confidence interval [CI], 1.04-1.60; P=2×10(-2); and OR, 2.22; 95% CI, 1.69-2.92; P=7×10(-9); respectively). When considering IPF and "other ILD" (non-IPF) separately, rs35705950 had a stronger association with IPF (OR, 3.2; 95% CI, 2.21-4.63; P=1.2×10(-10)) than with other ILD (OR, 1.72; 95% CI, 1.22-2.42; P=1.2×10(-3)). In contrast, rs2736100 was associated with other ILD (OR, 1.43; 95% CI, 1.11-1.85; P=6.2×10(-3)) but not with IPF (OR, 1.08; 95% CI, 0.78-1.49; P>0.05). Rs35705950 correlated significantly with increased pulmonary function (P<0.05). It was also associated with ILD without airflow obstruction in both the IPF and other ILD groups (P<0.01 for both), and conferred the highest risk for IPF without airflow obstruction (OR, 4.46; 95% CI, 2.60-7.66; P=4.5×10(-9)). Our study suggests that although both loci confer independent risks for ILD, rs35705950 may, in particular, contribute differentially to IPF and other ILD entities. Our study further highlights the genetic and phenotypic heterogeneity of ILD.

The Influence of Alternative Instruction on 6-Min Walk Test Distance

The goal of the 6-min walk test (6MWT) is to enable patients to walk "as far as possible" as a measure of their functional ability. The impact of the specific walk instructions on patient 6MWT performance is unknown. Patients with pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and other forms of interstitial lung disease (ILD) were recruited to perform four identical 6MWTs with one differing instructional phrase. The standard instruction to walk "as far as possible" was substituted in random order with "as fast as possible," "at your normal pace," or "at a leisurely pace." Twenty-four patients (10 with PAH, eight with IPF, six with other ILD) were enrolled and completed all four 6MWTs. Patients attained the greatest distance with the fast instruction, exceeding the standard instruction distance by a mean of 52.7 m (P < .001). The mean difference between the fast and standard walks was 41.5 m in the PAH group, 66.5 m in the IPF group, and 53 m in the other ILD group. Patients do not walk as far as they are able with the standard American Thoracic Society instruction for 6MWT. Changing the wording from "far" to "fast" may facilitate a better effort and greater distance during the test. It is possible that this modified 6MWT instruction may result in improved accuracy and reproducibility, thereby enhancing its clinical and research trial usefulness.

Intrapulmonary concentration of levofloxacin in patients with idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) have significantly impaired pulmonary diffusion, which may affect the pulmonary concentration of many drugs, including antibiotics. In this study, we compared the difference in pulmonary levofloxacin (LVFX) concentration between patients with normal lung function and IPF. The IPF group included 10 patients with a proven diagnosis of IPF and a diffusing capacity for carbon monoxide ranging from 40% to 70% of predicted values. The control group included 10 patients with normal pulmonary function. Blood and bronchoalveolar lavage fluid (BALF) were taken at 3–3.5 h after fasting. LVFX (500 mg) was administered orally. LVFX concentrations in the serum and BALF were determined using HPLC-MS/MC. The level of LVFX in alveolar epithelial lining fluid (ELF) was calculated using the following formula: LVFX ELF = LVFX BALF × (Urea serum/Urea BALF). No significant differences in age, body weight, height, and calculated creatinine clearance and BALF retrieval rate were observed between groups. LVFX serum concentrations in the IPF and control groups were (5.97 ± 1.28) μg/ml and (6.84 ± 3.43) μg/ml, respectively (P = 0.4727). ELF concentration of LVFX in the control group was (27.81 ± 21.36) μg/ml, while the concentration in the IPF group was (10.17 ± 2.46) μg/ml, less than half of that in the controls (P = 0.0058). The intrapulmonary concentration of LVFX in IPF patients was lower than those with normal lung function. Notably, however, the ELF LVFX concentration following 500 mg once-daily exceeded the MIC90 of common respiratory pathogens. Excellent antibacterial efficacy of LVFX can be expected for IPF patients in the treatment of respiratory tract infections.

Idiopathic Pulmonary Fibrosis and Gastroesophageal Reflux. Implications for Treatment

BackgroundEven though the pathogenesis of idiopathic pulmonary fibrosis (IPF) is unknown, there is mounting evidence that abnormal reflux (GERD) and aspiration of gastric contents may play a role in the pathogenesis of this disease. AimsThe aims of this study were to determine in patients with GERD and IPF: (a) the clinical presentation, (b) the esophageal function, and (c) the reflux profile. MethodsWe compared the clinical presentation, the esophageal function (as defined by high-resolution manometry), and the reflux profile (by dual sensor pH monitoring) in 80 patients with GERD (group A) and in 22 patients with GERD and IPF (group B). ResultsHeartburn was present in less than 60 % of patients with GERD and IPF. Lower esophageal sphincter pressure and peristalsis were normal in both groups, while the upper esophageal sphincter (UES) was more frequently hypotensive in IPF patients (p = 0.008). In patients with GERD and IPF, the proximal esophageal acid exposure was higher (p = 0.047) and the supine acid clearance was slower as compared with patients with GERD only (p < 0.001). ConclusionsThe results of this study show that in patients with GERD and IPF: (a) reflux is frequently silent, (b) with the exception of a weaker UES, the esophageal function is preserved, and (c) proximal reflux is more common, and in the supine position, it is coupled with a slower acid clearance. Because these factors predisposing IPF patients to the risk of aspiration, antireflux surgery should be considered early after the diagnosis of IPF and GERD is established.

Influence of radiological emphysema on lung function test in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is one of the most frequent interstitial lung disease. Emphysema can be associated with IPF as described in the «Combined pulmonary fibrosis and emphysema» syndrome. The primary endpoint of this retrospective cohort study was to evaluate the impact of the association of IPF and emphysema on lung function tests parameters (FVC, TLC, FEV1, FEV1/FVC and DLCO). The secondary endpoint was to assess the impact of the associated radiological emphysema on lung function parameters used in the du Bois prognostic score recently developed by Ron du Bois etal. We retrospectively reviewed the medical files of 98 patients with lung fibrosis who were followed in our University Hospital with access to pharmacological studies and lung transplantation from 1981 to 2011. Fifty six patients were considered for analysis. The collected data included gender, age, smoking history and respiratory hospitalizations. We also analysed their pulmonary functional parameters along with radiological characteristics, in particular the presence of emphysema which was assessed on thoracic high resolution CT scan. The du Bois score was retrospectively calculated from these data. TLC and FVC at diagnosis were significantly higher in the IPF-E group compared to the IPF group (respectively 86.6±17.2% pv versus 72.0±15.0% pv; p: 0.004 and 86.8±18.4% pv versus 72.6±20.6% pv; p: 0.020). The [Formula: see text] used in the calculation of the du Bois prognostic score was significantly higher in the IPF-E group. By cons, [Formula: see text] was not statistically different between the two groups. Radiological emphysema associated with IPF had an impact on pulmonary function tests. Despite this difference, the du Bois score was not statistically different between these two groups. Nevertheless, after one year of follow up, the patients with emphysema were in a subclass with a lower mortality rate than those without emphysema.

Idiopathic pulmonary fibrosis as a prognostic factor in non-small cell lung cancer

We investigated the postoperative mortality and long-term survival of lung cancer patients with underlying idiopathic pulmonary fibrosis (IPF). The data of 387 primary lung cancer patients treated by surgical resection at our hospital between 1995 and 2008 were retrospectively reviewed. Clinicopathological characteristics such as age, gender, survival, presence/absence of underlying IPF, atypical adenomatous hyperplasia (AAH), and the associations among these factors were examined. Among the 387 patients, 65 (16.8 %) had underlying IPF as detected by histopathology of the resected specimen (IPF group). The percentages of men and squamous cell carcinomas were significantly higher in the IPF group. None of our patients showed concomitant presence of AAH and IPF. Four of the 65 patients showed acute exacerbation of the IPF postoperatively, and all 4 of these patients died in hospital. In patients with non-small cell lung carcinoma, the postoperative survival tended to be lower in the IPF group than in the non-IPF group. Analysis using a Cox proportional hazards model by disease stage revealed that presence of underlying IPF was a risk factor for postoperative mortality in patients with pathological stage I/II but not for stage III/IV. Respiratory failure was the second main cause of death in the stage I/II lung cancer patients of the IPF group. Histopathological evidence of IPF was a risk factor for postoperative mortality and poor long-term survival, especially in patients with stage I/II non-small cell lung cancer, with postoperative respiratory failure representing the major cause of death.

Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis

BackgroundA polymorphism (rs35705950) 3 kb upstream of MUC5B, the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We...

Association of genetic polymorphisms of angiotensin converting enzyme and matrix metallo proteinase-1 with idiopathic pulmonary fibrosis

To investigate the correlation between angiotensin converting enzyme (ACE) and matrix metallo proteinase (MMP)-1 gene polymorphisms and the risk of idiopathic pulmonary fibrosis (IPF) in a Han Chinese population from Hebei Province. Eighty-four IPF patients and 100 controls were enrolled from the Second Hospital of Hebei Medical University. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect ACE gene insertion/deletion (I/D) polymorphism and MMP-1 polymorphism respectively. The MMP-1 polymorphism was genotyped by DNA sequence analysis. Radioimmunoassay and ELISA were used to analyzed AngII, MMP-1 and TIMP-1 levels in IPF patients and healthy controls. There was a significant difference between the 2 groups in allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism; frequency distribution of DD genotype and D allele of IPF patients were higher than those of the healthy control group (χ(2) = 11.227, 4.318, P < 0.05). There was no difference from different genders and ages on allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism. (χ(2) = 0.03 - 1.069, P > 0.05). There was no significant difference between the 2 groups in genotype and allele frequency distribution of MMP-1 1G/2G polymorphism (χ(2) = 0.94 and 0.001, P > 0.05). The AngII levels from DD genotype of both IPF patients and healthy controls were the highest, followed by the DI genotype and the II genotype. The AngII level of any genotype for ACE Insertion/Deletion polymorphism in the IPF group was higher than that in the healthy control group (all P < 0.05). The serum level of AngII, MMP-1 and TIMP-1, as well as MMP-1/TIMP-1 ratio in the IPF group were higher than those in the healthy control group (all P < 0.05). The ACE polymorphism might be associated with IPF, and the serum level of AngII was affected not only by the genetic background of ACE insertion/deletion polymorphism but also the environmental factors. The MMP-1 1G/2G polymorphism might be weakly associated with IPF.

Comparison of Characteristics of Connective Tissue Disease-Associated Interstitial Lung Diseases, Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Diseases, and Idiopathic Pulmonary Fibrosis in Chinese Han Population: A Retrospective Study

Our study compared the prevalence and characteristics of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD), or idiopathic pulmonary fibrosis (IPF) between January 2009 and December 2012 in West China Hospital, western China. Patients who met the criteria for ILD were included and were assigned to CTD-ILD, UCTD-ILD, or IPF group when they met the criteria for CTD, UCTD, or IPF, respectively. Clinical characteristics, laboratory tests, and high-resolution CT images were analyzed and compared among three groups. 203 patients were included, and all were Han nationality. CTD-ILD was identified in 31%, UCTD-ILD in 32%, and IPF in 37%. Gender and age differed among groups. Pulmonary symptoms were more common in IPF, while extrapulmonary symptoms were more common in CTD-ILD and UCTD-ILD group. Patients with CTD-ILD had more abnormal antibody tests than those of UCTD-ILD and IPF. Little significance was seen in HRCT images among three groups. A systematic evaluation of symptoms and serologic tests in patients with ILD can identify CTD-ILD, UCTD-ILD, and IPF.

HLA-A and HLA-B gene polymorphism and idiopathic pulmonary fibrosis in a Han Chinese population

Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse interstitial lung disease with poor prognosis of unknown etiology that leading ultimately to death. Predisposing factors are thought to have environmental and genetic inputs. We investigated the relationship between HLA-A, B gene polymorphism and idiopathic pulmonary fibrosis (IPF) in a Han Chinese population. The gene frequency of 36 patients with IPF was detected using a PCR-SSP grouping method. These values were compared with those a Bone Marrow Bank (Shanghai, China) of healthy subjects of identical racial origin as the patient group. The gene frequency of HLA-A*3 (3.5%), HLA-B*14 (1.4%), -B*15 (10.2%), and -B*40 (5.0%)of the IPF group increased significantly (Pc<0.05) compared with that in the control group HLA-A*3 (1.0%), HLA-B*14 (0.1%) and -B*15 (1.1%) and -B*40 (0.8%). Investigation of the link between the HLA-A and -B gene showed the gene frequency of HLA-A2B15 to be 5.0% as well as -A2B40 (4.3%), -A11B15 (5.0%), -A24B48 (2.8%) and -A30B40 (2.8%), which were significantly higher than those of the control group (Pc<0.05). These data suggest that the gene frequency of HLA-A*3, HLA-B*14, -B*15, -B*40, and the linked gene frequency of HLA-A2B15, -A2B40, -A11B15, -A24B58, -A30B40 is associated with IPF pathogenesis.