Idiopathic Pulmonary Fibrosis Cases Research Articles

Air trapping in usual interstitial pneumonia pattern at CT: prevalence and prognosis

This study was conducted to evaluate the presence of air trapping in patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs) (non-IPF), showing the radiological pattern of usual interstitial pneumonia (UIP). Retrospectively, we included 69 consecutive patients showing the typical UIP pattern on computed tomography (CT), and 15 final diagnosis of IPF with CT pattern “inconsistent with UIP” due to extensive air trapping. Air trapping at CT was assessed qualitatively by visual analysis and quantitatively by automated-software. In the quantitative analysis, significant air trapping was defined as >6% of voxels with attenuation between −950 to −856 HU on expiratory CT (expiratory air trapping index [ATIexp]) or an expiratory to inspiratory (E/I) ratio of mean lung density >0.87. The sample comprised 51 (60.7%) cases of IPF and 33 (39.3%) cases of non-IPF ILD. Most patients did not have air trapping (E/I ratio ≤0.87, n = 53, [63.1%]; ATIexp ≤6%, n = 45, [53.6%]). Air trapping in the upper lobes was the only variable distinguishing IPF from non-IPF ILD (prevalence, 3.9% vs 33.3%, p < 0.001). In conclusion, air trapping is common in patients with ILDs showing a UIP pattern on CT, as determined by qualitative and quantitative evaluation, and should not be considered to be inconsistent with UIP. On subjective visual assessment, air trapping in the upper lobes was associated with a non-IPF diagnoses.

Application of cross-theoretical model to education in patients with idiopathic pulmonary fibrosis combined with gastroesophageal reflux

Objective To explore the effect of intertheoretical model on education in patients with idiopathic pulmonary fibrosis combined with gastroesophageal reflux. Methods A total of 80 cases of idiopathic pulmonary fibrosis combined with gastroesophageal reflux were selected from October 2015 to November 2016.According to the random number table method, they were divided into the control group and the observation group, 40 cases of each group.The control group was given conventional nursing.The observation group combined healthy education based on the cross-theoretical model.The nursing effect were compared and observed between the two groups. Results The blood PH, PaO2 and PaCO2 levels of the two groups were observed before nursing, and the differences were no statistically significant(P>0.05). The blood PH and PaO2 levels of the observation group after nursing were significantly higher than those of the control group, and the differences were statistically significant(P 0.05). The pulmonary function indexes FVC, DLCO, 6MWT and TLC were significantly higher in the observation group than in the control group, and the differences were statistically significant(P<0.05). The scores of acute exacerbation, hospitalization and dyspnea in the observation group were significantly lower than those in the control group, and the differences were statistically significant(P<0.05). Conclusion Patients with idiopathic pulmonary fibrosis combined with gastroesophageal reflux have the ideal effect of combining conventional nursing methods with healthy education based on cross-theoretical model, which is worthy of promotion and application. Key words: Trans-theoretical model; Idiopathic pulmonary fibrosis; Gastroesophageal reflux; Health education; Effect

Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis

BackgroundThe clinical-radiographic distinction between idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) is challenging. We sought to investigate the gene expression profiles of IPF and NSIP vs. normal controls.MethodsGene expression from explanted lungs of patients with IPF (n = 22), NSIP (n = 10) and from normal controls (n = 11) was assessed. Microarray analysis included Significance Analysis of Microarray (SAM), Ingenuity Pathway, Gene-Set Enrichment and unsupervised hierarchical clustering analyses. Immunohistochemistry and serology of proteins of interest were conducted.ResultsNSIP cases were significantly enriched for genes related to mechanisms of immune reaction, such as T-cell response and recruitment of leukocytes into the lung compartment. In IPF, in contrast, these involved senescence, epithelial-to-mesenchymal transition, myofibroblast differentiation and collagen deposition. Unlike the IPF group, NSIP cases exhibited a strikingly homogenous gene signature. Clustering analysis identified a subgroup of IPF patients with intermediate and ambiguous expression of SAM-selected genes, with the interesting upregulation of both NSIP-specific and senescence-related genes. Immunohistochemistry for p16, a senescence marker, on fibroblasts differentiated most IPF cases from NSIP. Serial serum levels of periostin, a senescence effector, predicted clinical progression in a cohort of patients with IPF.ConclusionsComprehensive gene expression profiling in explanted lungs identifies distinct transcriptional profiles and differentially expressed genes in IPF and NSIP, supporting the notion of NSIP as a standalone condition. Potential gene and protein markers to discriminate IPF from NSIP were identified, with a prominent role of senescence in IPF. The finding of a subgroup of IPF patients with transcriptional features of both NSIP and senescence raises the hypothesis that “senescent” NSIP may represent a risk factor to develop superimposed IPF.

Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next-generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss-of-function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes (CSF3R, DSP, and LAMA3) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47-fold (95%CI: 2.07-5.81, P=2.34×10-6 ) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF.

Clinical significance of myeloperoxidase-anti-neutrophil cytoplasmic antibody in idiopathic interstitial pneumonias

ObjectiveAlthough a possible association among myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA), microscopic polyangiitis (MPA), and idiopathic pulmonary fibrosis (IPF) has been suggested, the clinical significance of MPO-ANCA in idiopathic interstitial pneumonias (IIPs), including IPF and non-IPF, remains unclear. We aimed to investigate the frequency of MPO-ANCA positivity, as well as MPA incidence and risk factors for development in patients initially diagnosed with IIP.MethodsWe retrospectively analysed 305 consecutive patients who were initially diagnosed as IIP and had MPO-ANCA results available.ResultsOf the 305 patients, 26 (8.5%) were MPO-ANCA-positive. Baseline characteristics were similar between the MPO-ANCA-positive and -negative patients. The cumulative 5-year MPA incidence was 24.3% in the MPO-ANCA-positive patients and 0% in the -negative patients (P < 0.0001). MPO-ANCA was positive in 15 of 133 (11.3%) patients initially diagnosed with IPF and in 11 of 172 (6.3%) patients initially diagnosed with non-IPF (P = 0.56), with cumulative 5-year MPA incidence of 6.2% and 1.0%, respectively (P = 0.10). Multivariate analysis revealed that UIP pattern on HRCT (HR = 3.20, P < 0.01) and no treatment for IIP (HR = 3.52, P < 0.01) were independently associated with MPA development in MPO-ANCA-positive patients.ConclusionMPO-ANCA positivity was uncommon, but was associated with subsequent MPA development in patients initially diagnosed with IIP, including both IPF and non-IPF cases. The study suggested that attention should be paid to MPA development in MPO-ANCA-positive IIP patients with UIP pattern on HRCT and those without treatment for IIP.

The Four Corners Sign: A Specific Imaging Feature in Differentiating Systemic Sclerosis-related Interstitial Lung Disease From Idiopathic Pulmonary Fibrosis.

Differentiating between systemic sclerosis-related interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is important because of the differences in workup, prognosis, and treatment. However, there is much overlap in the appearance of these 2 entities on high-resolution computed tomography. We propose that inflammation and/or fibrosis focally or disproportionately involving the bilateral anterolateral upper lobes and posterosuperior lower lobes ["Four Corners" Sign (FCS)] is specific for SSc-ILD. Randomized high-resolution computed tomography studies from 74 IPF and 73 SSc-ILD cases were evaluated by 2 thoracic radiologists blinded to all patient data. For each case the reviewers noted whether the FCS was present and assigned a confidence level on the basis of a 7-point Likert scale. The same process was then performed on a randomized external validation group of 42 SSc-ILD and 42 IPF cases. For Likert scores of 6 or 7 ("mostly agree" or "entirely agree" that the FCS is present, respectively) the sensitivity in SSc was 16.4% (95% confidence interval, 9.7%, 26.6%), specificity 100.0% (95% confidence interval, 95.1%, 100.0%). There was a significant association between a confidently present FCS and SSc compared with a confidently present FCS and IPF (P=0.0003). Analysis on an external validation group of 42 SSc and 42 IPF cases conferred similarly high specificity for SSc in cases characterized as FCS with high confidence. The FCS, a pattern of focal or disproportionate inflammation and/or fibrosis involving the bilateral anterolateral upper lobes and posterosuperior lower lobes, is specific for SSc-ILD when readers are confident of its presence.

Comorbidities and risk of mortality among hospitalized patients with idiopathic pulmonary fibrosis in Spain from 2002 to 2014.

To describe and compare the comorbid conditions, the in-hospital mortality (IHM) and the length of hospital stay (LOHS) among idiopathic pulmonary fibrosis (IPF) patients and non-IPF-matched patients hospitalized in Spain. We assess the performance of the Charlson Comorbidity Index[CCI] and the Elixhauser Comorbidity Index[ECI] to predict IHM in IPF and we identify the specific predictive factors of IHM in patients suffering IPF. We identified patients with IPF hospitalized in years 2002, 2006, 2010 and 2014. Cases of IPF were matched with non-IPF controls by sex, age, province of residence and year. Data were collected from the Spanish National Hospital Discharge Database. We identified 10,285 hospitalizations with IPF, evidencing an increase in the number of IPF patients from 2002 to 2014. Overtime the prevalence of comorbidities included in the CCI significantly increased in patients with IPF, exception made of myocardial infarction and dementia. The prevalence of comorbidities included in the ECI, except paralysis and peptic ulcer disease excluding bleeding, increased significantly overtime. LOHS was longer among IPF patients than non-IPF controls and decreased significantly from 2002 to 2014. IHM was significantly higher in patients with IPF (adjustedOR 1.97; 95%CI 1.77-2.19). Area under the ROC curves showed that ECI model had a better performance to predict IHM than CCI. The incidence of hospitalizations for IPF increased significantly from 2002 to 2014. We observed an increase overtime of most of the comorbidities included in CCI and ECI. LOHS and IHM were higher in patients with IPF than in non-IPF controls.

Incidence, Prevalence, and Survival of Patients with Idiopathic Pulmonary Fibrosis in the UK.

IntroductionRecent developments in the care of patients with idiopathic pulmonary fibrosis have the potential to improve survival rates. Population-based estimates of the current disease burden are needed to evaluate the future impact of newly approved therapies. The objective of this study is to describe incidence, prevalence, and survival of idiopathic pulmonary fibrosis patients in the UK.MethodsBetween 2000 and 2012, a patient cohort (N = 9,748,108), identified from Clinical Practice Research Datalink primary care data, was used to identify incident and prevalent cases of idiopathic pulmonary fibrosis–clinical syndrome. Incident cases were followed up to identify deaths. Poisson and Cox regressions were used to calculate incidence rate ratios (IRR) and hazard ratios for mortality, respectively. Adjustments were made for age, gender, and strategic health authority. Survival from diagnosis was estimated using Kaplan–Meier analysis.ResultsIn total 1491 and 4527 incident cases were identified using narrow and broad idiopathic pulmonary fibrosis–clinical syndrome definitions, respectively. Incidence and prevalence increased during the study. Compared with 2000, a near 80% increase in incidence was observed by 2012 [IRR 1.78 (95% CI 1.50–2.11; broad definition)], despite an observed decrease using the narrow definition [0.50 (0.38–0.65)]. Median survival was 3.0 years (95% CI 2.8–3.1) and 2.7 years (95% CI 2.5–3.0) in broad (n = 2168) and narrow case sets (n = 996), respectively. No significant changes in survival were observed.ConclusionsIdiopathic pulmonary fibrosis incidence rates have increased since 2000 and survival remains poor. These results provide a benchmark against which the effects of future treatment changes can be measured.FundingInterMune UK and Ireland (now part of F. Hoffman La Roche).Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0693-1) contains supplementary material, which is available to authorized users.

Modulation of Myeloid Cell Recruitment and Activation By Alveolar Epithelial Type 2 Cells Drives Early Inflammation in a Murine Model of Mutant Surfactant Protein‐C Pulmonary Fibrosis

The missense isoleucine to threonine substitution at position 73 [I73T] in the Surfactant Protein‐C [SP‐C] gene [SFTPC], an alveolar type‐2 cell [AT2] restricted protein, has been linked to sporadic and familial cases of idiopathic pulmonary fibrosis (IPF). Many patients with idiopathic pulmonary fibrosis (IPF) experience one or more episodes of precipitous deterioration. These “acute exacerbations” are marked by altered gas exchange, neutrophilic/eosinophilic alveolitis, diffuse alveolar damage, and changes on HRCT. To temporally model the impact of SP‐CI73T expression on lung homeostasis, we generated an inducible SP‐CI73T expressing line (IER‐SP‐CI73T) by crossing a hypomorphic SP‐CI73T‐Neo founder line to a R26FlpOER line. Intraperitoneal tamoxifen administration to hypomorphic IER‐SP‐CI73T mice resulted in early increases in mutant sftpcI73T mRNA and proSP‐CI73T protein expression accompanied by allele and tamoxifen dose dependent weight loss and mortality. In this early phase (3–14 d), IER‐SP‐CI73T mice exhibited histological evidence of diffuse lung injury, increased vascular leak, elevations in total bronchoalveolar lavage (BAL) cell counts, and distinct temporal increases in BAL MCP‐1, IL‐5, Eotaxin, IL‐6, CCL‐17, KC/CXCL‐1 and TGF‐β. By 6 weeks, lungs of surviving IER‐SP‐CI73T mice showed marked alveolar septal thickening, diffuse collagen deposition, and foci of αSMA+ cells consistent with an IPF phenotype. RNA‐sequencing profiling and PCR analysis of AT2 cells from IER‐SP‐CI73T mice confirmed an epithelial contribution to these recruitment and activation factors starting at 3d. To test the downstream effects of AT2‐effector cell crosstalk, we analyzed BAL and whole lung digests via flow cytometry. Tamoxifen induction resulted in sequential accumulation of SiglecFloCD11b+CD64−CD11c−Ly6C+ monocytes (3d), LY6G+ neutrophils (7d) and SiglecFhiCD11bhiCD11clo eosinophils (2wk) in the lung. Conversely, there was significant reduction in the number of SiglecFhiCD11bintCD64hiCD11chiCD206hi resident macrophages in lung tissue digests of IER‐SP‐CI73T mice. Intratracheal and intravenous clodronate depletion was used to test the role of resident macrophages and infiltrating monocytes, respectively, in the development of the injury. Notably, early intratracheal clodronate administration was associated with enhanced mortality, corroborating the notion that resident alveolar macrophages are fundamental in the early inflammatory response and crosstalk with lung epithelia. Conversely, monocyte depletion via IV clodronate appeared to be beneficial with respect to survival and BAL cell counts at 3d and 7d suggesting a deleterious role for these proinflammatory infiltrating cells in SP‐CI73T mediated lung injury. Taken together, our findings support the concept that epithelial dysfunction is a key component of IPF and highlights the importance of AT2 crosstalk with immune compartments in the lung to mediate blood borne cell recruitment, as well as modulate the resultant acute exacerbations and fibrotic remodeling.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dental Personnel Treated for Idiopathic Pulmonary Fibrosis at a Tertiary Care Center - Virginia, 2000-2015.

In April 2016, a Virginia dentist who had recently received a diagnosis of idiopathic pulmonary fibrosis (IPF) and was undergoing treatment at a specialty clinic at a Virginia tertiary care center contacted CDC to report concerns that IPF had been diagnosed in multiple Virginia dentists who had sought treatment at the same specialty clinic. IPF is a chronic, progressive lung disease of unknown cause and associated with a poor prognosis (1). Although IPF has been associated with certain occupations (2), no published data exist regarding IPF in dentists. The medical records for all 894 patients treated for IPF at the Virginia tertiary care center during September 1996-June 2017 were reviewed for evidence that the patient had worked as a dentist, dental hygienist, or dental technician; among these patients, eight (0.9%) were identified as dentists and one (0.1%) as a dental technician, and each had sought treatment during 2000-2015. Seven of these nine patients had died. A questionnaire was administered to one of the living patients, who reported polishing dental appliances and preparing amalgams and impressions without respiratory protection. Substances used during these tasks contained silica, polyvinyl siloxane, alginate, and other compounds with known or potential respiratory toxicity. Although no clear etiologies for this cluster exist, occupational exposures possibly contributed. This cluster of IPF cases reinforces the need to understand further the unique occupational exposures of dental personnel and the association between these exposures and the risk for developing IPF so that appropriate strategies can be developed for the prevention of potentially harmful exposures.

Increased Primary Cilia in Idiopathic Pulmonary Fibrosis.

Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue. Then, we investigated the distribution of primary cilia in human IPF tissue samples using immunofluorescence. Tissues from six IPF cases showed an increase in the number of primary cilia in alveolar cells and fibroblasts. In addition, we observed an increase in ciliogenesis related genes such as IFT20 and IFT88 in IPF. Since major components of the SHH signaling pathway are known to be localized in primary cilia, we quantified the mRNA expression of the SHH signaling components using qRT-PCR in both IPF and control lung. mRNA levels of SHH, the coreceptor SMO, and the transcription factors GLI1 and GLI2 were upregulated in IPF compared with control. Furthermore, the nuclear localization of GLI1 was observed mainly in alveolar epithelia and fibroblasts. In addition, we showed that defective KIF3A-mediated ciliary loss in human type II alveolar epithelial cell lines leads to disruption of SHH signaling. These results indicate that a significant increase in the number of primary cilia in IPF contributes to the upregulation of SHH signals.

Clinical and economic burden of idiopathic pulmonary fibrosis in Quebec, Canada.

BackgroundIdiopathic pulmonary fibrosis (IPF), although rare, is a severe and costly disease.ObjectiveTo estimate the clinical and economic burden of IPF over multiple years before and after diagnosis using comprehensive administrative databases for the province of Quebec, Canada.MethodsSeveral administrative databases from Quebec, providing information on hospital care, community care, and pharmaceuticals, were linked over a 5-year period ending March 31, 2011, which was before approval of antifibrotic drugs in Canada. Prevalent and incident IPF cases were defined using International Classification Disease-10-CA codes and International Classification Disease-9-CM codes. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases and a narrow definition that required further diagnostic testing to confirm IPF diagnosis. Incident cases had an IPF code in a particular year without any IPF code in the 2 previous years. Health care resource utilization before and after the index diagnosis date was determined and costs calculated. Costs were expressed in 2016 Canadian dollars.ResultsOver 5-years, 10,579 (mean age: 76.4; 58% male) satisfied the broad definition of IPF and 8,683 (mean age: 74.5; 57% male) satisfied the narrow definition (82% of broad). Incidences of IPF overall were 25.8 and 21.7/100,000 population for broad and narrow definitions, respectively. Three-year survival was 40% and 37% in broad and narrow cohorts, respectively. For both cohorts, health care resource utilization and costs increased several years before diagnosis ($2,721 and $7,049/patient 5 years and 2 years prior to diagnosis using a broad definition, respectively) and remained elevated for multiple years post diagnosis ($12,978 and $8,267 at 2 and 3 years postdiagnosis).ConclusionHealth care resource utilization and costs of IPF increase many years prior to diagnosis. Incorporating multiyear annual costs before and after diagnosis results in a higher estimate of the economic burden of IPF than previous studies using a 1-year time frame.

Burden of sleep-related breathing disorders, air trapping, and obesity in idiopathic pulmonary fibrosis patie

Background and aim Studies addressing the burden of sleep-related breathing disorders (SRBD) and evaluating polysomnography data in patients with idiopathic pulmonary fibrosis (IPF) are scarce. This work aims to illuminate the prevalence of SRBD in IPF patients, explore the effect of IPF on polysomnographic variables, and to identify the possible associations with air trapping and obesity. Patients and methods Institutional Review Board approval and formal patients’ consent were obtained from 39 patients enrolled in the study. Twenty patients were confirmed as IPF cases and 19 normal age-matched and sex-matched controls. Overnight polysomnography was performed to all patients. Pulmonary function test and high-resolution computed tomography were done for IPF cases. Results Half of IPF patients suffered from obstructive sleep apnea. Sleep efficiency, minimum SpO2, and baseline O2 saturation were significantly lower among IPF cases compared with controls (P Conclusion SRBD is of high prevalence in IPF patients and obesity is an insignificant comorbidity. Air trapping is surprisingly beneficial in IPF patients by maintaining oxygen saturation during sleep. Detection and proper treatment of comorbid SRBD may improve the natural course of this fatal illness.

Protein Folding and the Challenges of Maintaining Endoplasmic Reticulum Proteostasis in Idiopathic Pulmonary Fibrosis.

Alveolar epithelial type II (AEII) cells are "professional" secretory cells that synthesize and secrete massive quantities of proteins to produce pulmonary surfactant and maintain airway immune defenses. To facilitate this high level of protein synthesis, AEII cells are equipped with an elaborate endoplasmic reticulum (ER) structure and possess an abundance of the machinery needed to fold, assemble, and secrete proteins. However, conditions that suddenly increase the quantity of new proteins entering the ER or that impede the capacity of the ER to fold proteins can cause misfolded or unfolded proteins to accumulate in the ER lumen, also called ER stress. To minimize this stress, AEII cells adapt by (1) reducing the quantity of proteins entering the ER, (2) increasing the amount of protein-folding machinery, and (3) removing misfolded proteins when they accumulate. Although these adaptive responses, aptly named the unfolded protein response, are usually effective in reducing ER stress, chronic aggregation of misfolded proteins is recognized as a hallmark feature of AEII cells in patients with idiopathic pulmonary fibrosis (IPF). Although mutations in surfactant proteins are linked to the development of ER stress in some rare IPF cases, the mechanisms causing protein misfolding in most cases are unknown. In this article, we review the mechanisms regulating ER proteostasis and highlight specific aspects of protein folding and the unfolded protein response that are most vulnerable to failure. Then, we postulate mechanisms other than genetic mutations that might contribute to protein aggregation in the alveolar epithelium of IPF lung.

The Development of a Respiratory Nurse Led Clinic in St Michael’s Hospital

Introduction: Patients referred by their GP with a suspected respiratory problem have a long wait for a specialist respiratory review which can have a detrimental effect on morbidity and mortality 1. Description of practice change implemented: In 2013 we developed an integrated nurse led respiratory clinic for patients referred by their general practitioner (GP) with new respiratory problems. A respiratory consultant screens all referrals for suitability. The assessment includes history taking, examination and education by the nurse. In one visit, the patient will have investigations such as spirometry with reversibility, alpha 1 antitrypsin testing, BNP, oxygen assessment (and ABG if appropriate), walking test, CXR and ECG. Subsequently, the nurse discusses findings with a respiratory consultant and develops a plan of care. A report is then sent to the GP. Aim and theory of change/ Targeted population and stakeholders: The aims and objectives were to provide a high standard nursing service to patients that encompassed their physical, psychological and social needs. The service aimed to integrate primary and secondary care by providing rapid assessment for patients referred by their general practitioners with new respiratory symptoms. As a result this service was predicted to reduce the nine month waiting list for the physician led respiratory clinic. Highlights: (innovation, Impact and outcomes) Of the patients (320) reviewed, 57% had COPD, 21% had Asthma and the large majority of the remaining patients had no significant respiratory problem. There were two cases of idiopathic pulmonary fibrosis and three cases of lung cancer. 73% of patients were discharged back to their GP, 5% were referred to the physician-led clinic and the remaining 22% are still attending the clinic. Savings are generated through avoidance of multiple outpatient attendances, less dependence on physicians and optimisation of medication prescription and delivery. Patients benefitted through early diagnosis and treatment in a single visit to a clinic. Waiting times for physician review have now reduced from nine months in 2013 to two months in 2016). This service is transferable to all hospitals that provide specialist respiratory care. To ensure safety and quality it is recommended that the clinical nurse specialist that carries out the clinic be academically qualified up to masters level and have training in advanced health assessment skills. We conclude that integrated nurse led clinics are associated with high levels of patient satisfaction.

Safety study of autologous adult bone marrow derived mesenchymal stromal cells in idiopathic pulmonary fibrosis - Pilot data

BackgroundLung transplantation is the choice of therapy in severe cases of idiopathic pulmonary fibrosis (IPF) but is compounded with post-transplant complications. The paucity of deceased organ donations underlines the need for alternate approaches that improves the quality of life. Herein, we attempted to develop an autologous adult bone marrow derived mesenchymal stromal cell (BMSC) therapy via central line access, and evaluated the safety of a single dose (~13 × 106cells/mL), in treating “no option” IPF. MethodThe study included severe IPF subjects (n = 6) both male and female, aged 40–70 years of age with a forced vital capacity <50%, diffusing capacity of lung for carbon monoxide (DLco) <35% of predicted, and/or oxygen (SpO2) saturation <88% on 6min walk distance (6 MWD). BMSCs at passage 2 were suspended in 30.0mL normal saline and dispensed through the central line route in a respiratory intensive care unit of Gleneagles Global Hospitals. The subjects were monitored for the first 24h for serious adverse events and hemodynamic parameters. They were followed up periodically at intervals of 1, 4, and 9 months for safety and monitoring of adverse events, including secondary objectives of changes in pulmonary function test, DLco, 6 MWD, and quality of life as per the study protocol. ResultsIt was observed that central line infusions were well tolerated by all subjects. Furthermore, there was an improved quality of life. ConclusionsBMSC central line infusion in “no option” IPF cases provided an insight into the strategies in improving the quality of life for patient and thereby increasing the therapeutic window period for lung transplantation.

Low body surface area predicts hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis

After the commercialization of nintedanib in Japan, a high incidence of hepatotoxicity resulting in treatment interruption was noted in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib in our hospital. This study aimed to clarify the risk factors for hepatotoxicity of nintedanib. Sixty-eight consecutive cases of IPF newly treated with nintedanib at a dose of 150 mg twice daily from September 2015 to September 2016 were enrolled: 46 patients (67.6%) exhibited aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) elevation and 16 patients (23.5%) also had a Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2. Body surface area (BSA) was significantly lower in the CTCAE grade ≥2 group than in another group. A multivariate logistic regression analysis showed that the association between BSA and AST/ALT elevation with CTCAE grade ≥2 was statistically significant. Eight of 10 patients who resumed nintedanib at a reduced dose of 100 mg twice daily after interruption due to hepatotoxicity did not again develop AST/ALT elevation. In conclusion, a low BSA was associated with hepatotoxicity of nintedanib at a dose of 150 mg twice daily. It would be a good option for patients with a small physique to start nintedanib at a dose of 100 mg twice daily and then increase if possible after confirming its safety.

Reduced expression of BMP3 contributes to the development of pulmonary fibrosis and predicts the unfavorable prognosis in IIP patients.

Idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (INSIP) are two related diseases involving varying degrees of pulmonary fibrosis with no effective cure. Bone morphogenetic protein 3 (BMP3) is a member of the transforming growth factor-β (TGF-β) super-family, which has not been implicated in pulmonary fibrosis previously. In this study, we aimed to investigate the potential role of BMP3 playing in pulmonary fibrosis from clinical diagnosis to molecular signaling regulation. RNA sequencing was performed to explore the potential biomarker of IIP patients. The expression of BMP3 was evaluated in 83 cases of IPF and INSIP by immunohistochemistry. The function of BMP3 was investigated in both fibroblast cells and a bleomycin-induced murine pulmonary fibrosis model. The clinical relevance of BMP3 expression were analyzed in 47 IIP patients, which were included in 83 cases and possess more than five-year follow-up data. Both RNA-sequencing and immunohistochemistry staining revealed that BMP3 was significantly down-regulated in lung tissues of patients with IPF and INSIP. Consistently, lower expression of BMP3 also was found in pulmonary fibrotic tissues of bleomycin-induced mice model. Up-regulation of BMP3 prevented pulmonary fibrosis processing through inhibiting cellular proliferation of fibroblasts as well as TGF-β1 signal transduction. Finally, the relatively higher expression of BMP3 in IPF patients was associated with less/worse mortality. Intravenous injection of recombinant BMP3. Taken together, our results suggested that the low expression level of BMP3 may indicate the unfavorable prognosis of IPF patients, targeting BMP3 may represent a novel potential therapeutic method for pulmonary fibrosis management.

Code-based Diagnostic Algorithms for Idiopathic Pulmonary Fibrosis. Case Validation and Improvement.

Population-based studies of idiopathic pulmonary fibrosis (IPF) in the United States have been limited by reliance on diagnostic code-based algorithms that lack clinical validation. To validate a well-accepted International Classification of Diseases, Ninth Revision, code-based algorithm for IPF using patient-level information and to develop a modified algorithm for IPF with enhanced predictive value. The traditional IPF algorithm was used to identify potential cases of IPF in the Kaiser Permanente Northern California adult population from 2000 to 2014. Incidence and prevalence were determined overall and by age, sex, and race/ethnicity. A validation subset of cases (n = 150) underwent expert medical record and chest computed tomography review. A modified IPF algorithm was then derived and validated to optimize positive predictive value. From 2000 to 2014, the traditional IPF algorithm identified 2,608 cases among 5,389,627 at-risk adults in the Kaiser Permanente Northern California population. Annual incidence was 6.8/100,000 person-years (95% confidence interval [CI], 6.1-7.7) and was higher in patients with older age, male sex, and white race. The positive predictive value of the IPF algorithm was only 42.2% (95% CI, 30.6 to 54.6%); sensitivity was 55.6% (95% CI, 21.2 to 86.3%). The corrected incidence was estimated at 5.6/100,000 person-years (95% CI, 2.6-10.3). A modified IPF algorithm had improved positive predictive value but reduced sensitivity compared with the traditional algorithm. A well-accepted International Classification of Diseases, Ninth Revision, code-based IPF algorithm performs poorly, falsely classifying many non-IPF cases as IPF and missing a substantial proportion of IPF cases. A modification of the IPF algorithm may be useful for future population-based studies of IPF.

Spatial and temporal variability of idiopathic pulmonary fibrosis cases in Silesian Voivodeship in years 2006-2010.

Idiopathic pulmonary fibrosis (IPF) (J84.1 by the International Statistical Classification of Diseases and Related Health Problems, 10th revision - ICD-10) is a rare disease of unknown cause. Among many risk factors, occupational exposure to metal dust is enumerated. Because of metal industry concentration in the Silesian Voivodeship, Poland, an attempt of spatial and temporal variability of the idiopathic pulmonary fibrosis occurrence evaluation in 2006-2010 is made. The research is a descriptive analysis. Data of the number of new treated cases and firsttime hospitalization due to idiopathic pulmonary fibrosis in the years 2006-2010 was obtained from the National Health Found (Narodowy Fundusz Zdrowia - NFZ). We also assessed spatial and temporal variability of both rates. Data concerned adults aged ≥ 19 years old inhabited the Silesian Voivodeship. The standardized incidence rate due to idiopathic pulmonary fibrosis increased in the study period and was in the range of 2.9-3.8/100 000 population. The highest values of incidence were observed in districts localized in the centre of the Silesian Voivodeship. Incidence of idiopathic pulmonary fibrosis is not so high in the Silesian Voivodeship but the number of newly treated cases slightly increased in 2006-2010. Spatial and temporal variability of incidence rates for treated registered cases of idiopathic pulmonary fibrosis in the Silesian Voivodeship was observed. It could be an effect of occupational exposure to metal dust, however, final conclusions need more precise studies to the extent of analytical epidemiology. Int J Occup Med Environ Health 2017;30(4):593-601.