Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Collard, Harold R.; Moore, Bethany B.; Flaherty, Kevin R.; Brown, Kevin K.; Kaner, Robert J.; King, Talmadge E.; Lasky, Joseph A.; Loyd, James E.; Noth, Imre; Olman, Mitchell A.; Raghu, Ganesh; Roman, Jesse; Ryu, Jay H.; Zisman, David A.; Hunninghake, Gary W.; Colby, Thomas V.; Egan, Jim; Hansell, David M.; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kondoh, Yasuhiro; Lynch, David A.; Müller–Quernheim, Joachim; Myers, Jeffrey L.; Nicholson, Andrew G.; Selman, Moisés; Toews, Galen B.; Wells, Adrian; Martínez, Fernando J.

doi:10.1164/rccm.200703-463pp

Cited by 997 publications

(869 citation statements)

References 79 publications

(118 reference statements)

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“…Recent data have suggested that AE-IPF may be due to an acceleration of the underlying fibroproliferative disease process (Konishi et al 2009;Collard et al 2007). Finding higher pulmonary expression of HSP47, a collagen-specific molecular chaperone, in DAD than in UIP tissues in this study is consistent with that hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…The natural history of idiopathic pulmonary fibrosis (IPF) is complex, and many patients have an unpredictable disease course with periods of relative stability punctuated by episodes of acute and often fatal decline (Hyzy et al 2007;Collard et al 2007;Song et al 2010;Raghu et al 2011). This acute worsening of the disease is sometimes attributed to identifiable conditions such as pneumonia or heart failure.…”

Section: Introductionmentioning

confidence: 99%

“…Recent data have suggested that AE-IPF may be due to an acceleration of the underlying fibroproliferative disease process (Konishi et al 2009;Collard et al 2007); it is therefore assumed that HSP47 is also involved in its pathogenesis. Previous studies in several experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces production of collagen and subsequently diminishes progression of fibrosis (Sunamoto et al 1998;Nishino et al 2003;Hagiwara et al 2007a, b, c;Obata et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic differences involving HSP47 between AE-IPF and stable (S)-IPF. -013-0411-5 and lactate dehydrogenase (LDH) were measured. Immunohistochemical analysis of lung HSP47 expression was determined in biopsy and autopsy tissues diagnosed as diffuse alveolar damage (DAD) and usual interstitial pneumonia (UIP). Serum levels of HSP47 were significantly higher in AE-IPF than in S-IPF patients, whereas serum levels of KL-6, SP-A, and SP-D did not differ significantly. Receiver operating characteristic curves revealed that HSP47 was superior for discriminating AE-IPF and S-IPF. The cutoff for HSP47 resulting in the highest diagnostic accuracy was 559.4 pg/mL; sensitivity, specificity, and diagnostic accuracy were 100.0 %, 93.9 %, and 96.2 %, respectively. Immunohistochemical analysis revealed that pulmonary HSP47 expression was greater in DAD than UIP tissues. Serum HSP47 was significantly higher in AE-IPF than in S-IPF patients, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions.Cell Stress and Chaperones (2013) 18:581-590 DOI 10.1007/s12192

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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“…We divided progression of ILD into three categories; no progression, slow progression, and acute exacerbation. The definition of acute exacerbation or AE-ILD included a prior diagnosis of ILD, worsening of dyspnea within 1 month, new ground-glass opacities on HRCT, hypoxemia, and the exclusion of other causes for the worsening symptoms (Collard et al 2007). If repeated CT scan showed progression without fulfilling the definition of AE-ILD, we defined it as slow progression.…”

Section: Evaluation Of Ildmentioning

confidence: 99%

High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis

Tomiyama

Watanabe

Ishii

et al. 2016

Tohoku J. Exp. Med.

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Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by extensive fibrosis and autoantibodies. Its clinical manifestations are diverse and include Raynaud's phenomenon, gastrointestinal dysmotility, interstitial lung disease (ILD), pulmonary hypertension, and renal crisis. Among these, ILD is the primary cause of SSc-related death. It has been considered that acute exacerbation of ILD (AE-ILD) is not common in patients with SSc; however, little is known about the prevalence of AE-ILD in Japanese patients with SSc. In this study, we aimed to clarify the prevalence, clinical characteristics, and prognosis of patients with SSc who developed AE-ILD and to identify predictive factors for AE-ILD in our Japanese cohorts. Clinical data of patients who visited our department from 1990 to 2014 and fulfilled the 2013 classification criteria for SSc were retrospectively reviewed. A total of 139 patients were enrolled. The mean age of onset was 49.1 years, and 113 (81.3%) patients were female; 116 (83.5%) had limited cutaneous involvement, and the overall 10-year survival rate was 92.0%. Among 66 (47.5%) patients with ILD, 13 (9.4%) developed AE-ILD. Patients with AE-ILD had a significantly higher incidence of overlap with polymyositis (PM) or dermatomyositis (DM) and lower prevalence of anticentromere antibodies with higher mortality rate compared with those without AE-ILD. Multivariate Cox regression analysis identified that an overlap with PM or DM was the most significant predictive factor for AE-ILD. Our study results suggest that Japanese patients with SSc, particularly patients overlapped with PM or DM, have a high risk of AE-ILD.

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“…The Histopathological results and specific autoimmune markers were used for diagnosis of this group associated with the clinical and radiological picture of these patients. Exclusion criteria: IPF in acute exacerbation; defined by worsening of respiratory symptoms within 30 days, new bilateral ground glass opacities on HRCT, and no evidence of an alternative etiology [15].…”

Section: Patientsmentioning

confidence: 99%

Assessment of Bronchoalveolar Lavage Pepsin Level in Idiopathic Pulmonary Fibrosis

Said¹,

Alsowey²,

Ibraheem³

2017

Zagazig University Medical Journal

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Background: Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause.Recently, there is increasing evidence supporting a relationship between gastroesophageal reflux, microaspiration, and IPF, since the diagnostic gold-standard for microaspiration remains unknown. So, the aim of this study is to assess the presence of chronic microaspirates by bronchoalveolar lavage pepsin level in these patients. Patients and method: A case -control study was conducted at Chest Department and outpatient clinics Faculty of Medicine, Zagazig University hospitals in the period from (February 2013 till January 2016) on thirty patients with stable interstitial lung diseases (ILD).they were divided into two groups: 15 patients (group I) with stable idiopathic pulmonary fibrosis (IPF), another 15 patients (group II) stable ILD other than IPF. Both groups underwent pulmonary function tests (PFTs), Pulmonary HRCT and Bronchoscopy. Measurement of bronchoalveolar lavage pepsin level was done for all patients. Results: 80% of IPF patients complained from gastroesophageal reflux with a statistically significant decrease in PaO 2 , FEV 1 and FVC than in non IPF patients.Bronchoalveolar lavage pepsin level was (43.711.4ng/ml) in IPF group, which was significantly higher than non IPF group (32.710.5 ng/ml).Also total cell count in IPF patients were increased significantly including neutrophils, alveolar macrophages and red blood. Increased reticulation on HRCT for IPF patients group were associated with higher BAL pepsin levels (p <0.01). Regression coefficient revealed the most powerful predictor of IPF severity were; HRCT findings: reticulation score,honeycombing score[(Odds ratio(95%CI)=5.3 (1.9 to14.9), 7.8 (2.7 to 22.3)respectively],pepsin level[(Odds ratio(95%CI)=4.6 (1.9-11.4)],FEV1 and FVC[(Odds ratio(95%CI)=3.7 (1.6 to 8.9), 3.2 (1.4 to 7.5)respectively].while gastroesophageal reflux symptom [(Odds ratio(95%CI)=1.04(0.94-1.14)] was the least powerful predictor. Conclusion: Gastroesophageal reflux or microaspiration is common in patients with IPF, associated with elevated levels of pepsin in BAL fluid.

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Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Cited by 997 publications

References 79 publications

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis

Assessment of Bronchoalveolar Lavage Pepsin Level in Idiopathic Pulmonary Fibrosis

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