The pathogenesis of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an appalling prognosis. The failure of anti-inflammatory therapies coupled with the observation that deranged epithelium overlies proliferative myofibroblasts to form the fibroblastic focus has lead to the emerging concept that IPF is a disease of deregulated epithelial-mesenchymal crosstalk. IPF is triggered by an as yet unidentified alveolar injury that leads to activation of transforming growth factor-β (TGF-β) and alveolar basement membrane disruption. In the presence of persisting injurious pathways, or disrupted repair pathways, activated TGF-β can lead to enhanced epithelial apoptosis and epithelial-to-mesenchymal transition (EMT) as well as fibroblast, and fibrocyte, transformation into myofibroblasts which are resistant to apoptosis. The resulting deposition of excess disrupted matrix by these myofibroblasts leads to the development of IPF.     

特发性肺纤维化的治疗

特发性肺纤维化（IPF）又称隐原性致纤维化肺泡炎。IPF的病因不明，发病机制不甚明了，其确切发病率尚不清楚，国外报道约为十万分之五，但由于疗效差，其5年生存率低于50％。近年来IPF的发生有明显上升趋势，从而引起人们极大的关注。目前对IPF的治疗尚无确实、有效的方法，主要药物有糖皮质激素、免疫抑制剂药物、抗氧化剂和细胞因子拮抗剂等，但尚无任何治疗方案能改变或逆转IPF的炎症过程，更不能逆转纤维化性病变。近年来有关治疗研究的焦点开始从抗炎向抗纤维化转变，一些抗纤维化的药物，如吡非尼酮（pirfenidone）、γ干扰素1b等已显示出较理想的治疗前景。现将目前治疗IPF较为常用的方法和药物进行简单介绍。     

Corticosteroids in idiopathic pulmonary fibrosis

Corticosteroids were the mainstay of therapy for idiopathic pulmonary fibrosis (IPF) for more than four decades, but their efficacy is unproven and toxicities are substantial. The course of IPF is characterized by progressive respiratory insufficiency, leading to death within 3 to 8 years from the onset of symptoms. Although a subset (10-20%) of patients survives more than 10 years, there is no evidence that any form of therapy alters the natural history of the disease. Nonetheless, given the poor prognosis, a trial of corticosteroids is often given. Because of the rarity of IPF, randomized, placebo-controlled therapeutic trials have not been done. Further, no studies have compared differing dosages or duration of corticosteroid in matched patients. Interpretation of therapy efficacy is obscured by several factors including heterogeneous patient populations, inclusion of patients with histologic entities other than usual interstitial pneumonia, lack of objective, validated endpoints, different criteria for "response." We review published data regarding corticosteroid therapy for IPF and present a rationale for stratifying therapy based on host, demographic, and clinical factors that influence prognosis as well as risk for corticosteroid complications.     

Reassessment of the classification of the severity in idiopathic pulmonary fibrosis using SF-36 questionnaire

OBJECTIVE: To investigate whether or not the newly revised classification of the severity of idiopathic interstitial pneumonia (IIP) is appropriate with respect to quality of life (QOL). METHODS: The association between the subscale of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and pulmonary function or serum marker was analyzed using Pearson's correlation coefficient. The association between the subscale of SF-36 and the previous or newly revised classification of the severity of IIP was analyzed using Spearman's rank correlation test. PATIENTS: Forty patients with idiopathic pulmonary fibrosis (IPF) were enrolled. RESULTS: The mean deviation value scores for 7 items, excluding bodily pain (BP) in SF-36 were below the national reference values. % vital capacity (VC) was correlated with the 7 items excluding BP. However, neither serum LDH nor KL-6 values were correlated with any item in SF-36. According to the new or previous classification of the severity, severity was correlated with physical function, limitation of role functioning related physical problems and general health (GH); the correlation coefficient with the new one was slightly higher than the previous one. Based on these results, we established a unique draft on the classification of the severity. %VC <70% was added as an item for the newly revised classification in our draft. In our draft, there was rank correlation between the 7 items, excluding BP, in SF-36 and severity. CONCLUSION: With respect to QOL, the newly revised classification of the severity of IIP was not satisfactory, but the hypoxemia during exercise in patients with resting PaO(2) >80 Torr and reduction of VC were found to be important factors.     

Prediction of pulmonary hypertension in idiopathic pulmonary fibrosis

BACKGROUND: Reliable, noninvasive approaches to the diagnosis of pulmonary hypertension in idiopathic pulmonary fibrosis are needed. We tested the hypothesis that the forced vital capacity to diffusing capacity ratio and room air resting pulse oximetry may be combined to predict mean pulmonary artery pressure (MPAP) in idiopathic pulmonary fibrosis. METHODS: Sixty-one idiopathic pulmonary fibrosis patients with available right-heart catheterization were studied. We regressed measured MPAP as a continuous variable on pulse oximetry (SpO(2)) and percent predicted forced vital capacity (FVC) to percent-predicted diffusing capacity ratio (% FVC/% DL(co)) in a multivariable linear regression model. RESULTS: Linear regression generated the following equation: MPAP=-11.9+0.272 x SpO(2)+0.0659 x (100-SpO(2))(2)+3.06 x (% FVC/% DL(co)); adjusted R(2)=0.55, p<0.0001. The sensitivity, specificity, positive predictive and negative predictive value of model-predicted pulmonary hypertension were 71% (95% confidence interval (CI): 50-89%), 81% (95% CI: 68-92%), 71% (95% CI: 51-87%) and 81% (95% CI: 68-94%). CONCLUSIONS: A pulmonary hypertension predictor based on room air resting pulse oximetry and FVC to diffusing capacity ratio has a relatively high negative predictive value. However, this model will require external validation before it can be used in clinical practice.     

Management of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disorder characterized by progressive dyspnea, exercise intolerance and, ultimately, respiratory failure and death. The incidence of IPF seems to be increasing, whereas its etiology remains unelucidated. Agents capable of modulating inflammation, kinase pathways, vascular tone, coagulation and fibrosis have been tested in clinical studies although not always in large, randomized, placebo-controlled prospective trials. Despite this effort, a therapy capable of improving survival remains elusive. Consequently, the management of IPF focuses on the early identification of subjects for lung transplantation and on the treatment of comorbidities such as hypoxemia, cough and deconditioning. Until effective therapies are identified, patients and referring physicians are urged to consider participation in well-designed clinical trials.     

Treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive lung disease in most cases, and effective treatment is still lacking. This review examines the current status of treatment options and complexities in the management of patients with IPF. Although optimal therapy for IPF has not been identified, ongoing research efforts warrant reason for optimism. Current management of IPF includes not only judicious use of available pharmacological agents tailored to individual circumstances but also patient education through realistic assessment of prognosis, discussion of pros and cons of pharmacotherapy, early consideration of lung transplantation when applicable, treatment of complications, supportive care, and encouragement to participate in clinical trials.     

Management of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a deadly progressive lung disease without an effective standard treatment approach. Because of the complexity and uncertainties of IPF treatment, therapeutic decisions need to be tailored to the individual patient, after discussing the potential benefits and pitfalls. Pirfenidone has been approved for the treatment of IPF in many countries, but is not recommended as a first-choice therapy by current guidelines because of the lack of a definite efficacy. Randomized controlled trials represent a valid choice for patients with IPF, and their completion is important in improving both survival and quality of life.