特发性肺纤维化

一部分患者的疾病过程特征是间歇性的急性加重，伴突发性和永久性肺功能下降。[44]Collard HR, Moore BB, Flaherty KR, et al. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176:636-643.http://www.atsjournals.org/doi/full/10.1164/rccm.200703-463PP#.UmETsNglgZkhttp://www.ncbi.nlm.nih.gov/pubmed/17585107?tool=bestpractice.com

急性加重的特点是在过去的30天内呼吸困难加重，HRCT示典型的UIP基础上双侧新出现的磨玻璃影和/或实变。此外，没有证据支持肺部感染、左心衰竭、肺栓塞或其他可以引起急性肺损伤的病因。

可能需要机械通气，或者肺移植以挽救生命。

虽然缺乏支持的证据，高剂量糖皮质激素伴或不伴细胞毒性药物，通常用于急性加重的治疗。2011年ATS/ERS/JRS/ALAT指南弱推荐在IPF急性加重时使用糖皮质激素，但没有推荐使用细胞毒性药物。[46]Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824.http://www.thoracic.org/statements/resources/interstitial-lung-disease/ipf0311.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/21471066?tool=bestpractice.com2015 年 ATS/ERS/JRS/ALAT 指南并未解决这一问题。[58]Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis - an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192:e3-e19.https://www.thoracic.org/statements/resources/interstitial-lung-disease/IPF-Full-length.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26177183?tool=bestpractice.com这些患者的短期病死率，包括住院病死率很高。[82]Martinez FJ, Safrin S, Weycker D, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med. 2005;142:963-967.http://www.ncbi.nlm.nih.gov/pubmed/15968010?tool=bestpractice.com[83]Agarwal R, Jindal SK. Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review. Eur J Intern Med. 2008;19:227-235.http://www.ncbi.nlm.nih.gov/pubmed/18471669?tool=bestpractice.com

虽然缺乏支持的证据，高剂量糖皮质激素伴或不伴细胞毒性药物，通常用于急性加重的治疗。2011年ATS/ERS/JRS/ALAT指南弱推荐在IPF急性加重时使用糖皮质激素，但没有推荐使用细胞毒性药物。[46]Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824.http://www.thoracic.org/statements/resources/interstitial-lung-disease/ipf0311.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/21471066?tool=bestpractice.com2015 年 ATS/ERS/JRS/ALAT 指南并未解决这一问题。[58]Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis - an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192:e3-e19.https://www.thoracic.org/statements/resources/interstitial-lung-disease/IPF-Full-length.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26177183?tool=bestpractice.com

这些患者的短期病死率，包括住院病死率很高。[82]Martinez FJ, Safrin S, Weycker D, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med. 2005;142:963-967.http://www.ncbi.nlm.nih.gov/pubmed/15968010?tool=bestpractice.com[83]Agarwal R, Jindal SK. Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review. Eur J Intern Med. 2008;19:227-235.http://www.ncbi.nlm.nih.gov/pubmed/18471669?tool=bestpractice.com

在IPF患者中，应该强烈考虑应用吡非尼酮或尼达尼布治疗。ATS/ERS/JRS/ALAT 治疗指南有条件地推荐使用这些制剂。[58]Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis - an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192:e3-e19.https://www.thoracic.org/statements/resources/interstitial-lung-disease/IPF-Full-length.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26177183?tool=bestpractice.com

试验纳入轻到中度的IPF患者，定义为FVC预测值百分比至少50%，弥散量预测值百分比至少30%。[63]King TE Jr, Bradford WZ, Castro-Bernardini S, et al; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083-2092.http://www.ncbi.nlm.nih.gov/pubmed/24836312?tool=bestpractice.com[65]Richeldi L, du Bois RM, Raghu G, et al; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071-2082.http://www.ncbi.nlm.nih.gov/pubmed/24836310?tool=bestpractice.com治疗的其他方面，包括应该考虑个人的基础情况可能影响到患者。

吡非尼酮和尼达尼布没有进行过二者的直接对比，也没有联合治疗的研究。在决定使用吡非尼酮或尼达尼布时，应该考虑其有效性、患者的偏好和不良反应。

仍在吸烟的患者，应该建议戒烟。

肺康复项目可能使许多患者受益，改善他们的肺功能状态[79]Bott J, Blumenthal S, Buxton M, et al; British Thoracic Society Physiotherapy Guideline Development Group. Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient. Thorax. 2009;64(suppl 1):i1-i51.http://thorax.bmj.com/content/64/Suppl_1/i1.longhttp://www.ncbi.nlm.nih.gov/pubmed/19406863?tool=bestpractice.com和生活质量。[80]Dowman L, Hill CJ, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev. 2014;(10):CD006322.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006322.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25284270?tool=bestpractice.com综合进行运动训练、患者教育和社会心理支持，可能有助于提高除肺功能之外的运动耐力，2011年ATS/ERS/JRS/ALAT指南为弱推荐。[46]Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824.http://www.thoracic.org/statements/resources/interstitial-lung-disease/ipf0311.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/21471066?tool=bestpractice.com

在静息或运动时严重的低氧血症（动脉血氧分压≤55 mmHg，或血氧饱和度≤89%）应该进行氧疗，2011年ATS/ERS/JRS/ALAT指南为强推荐。[46]Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824.http://www.thoracic.org/statements/resources/interstitial-lung-disease/ipf0311.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/21471066?tool=bestpractice.com氧疗可以提高运动耐量，减少发生肺动脉高压和肺心病的风险。

针对经选择患者组全部患者的治疗推荐

ATS/ERS/JRS/ALAT 指南有条件地推荐，患有食管反流的患者应接受抑酸治疗，最好采用质子泵抑制剂。[58]Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis - an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192:e3-e19.https://www.thoracic.org/statements/resources/interstitial-lung-disease/IPF-Full-length.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26177183?tool=bestpractice.com

此外，一项IPF患者的回顾性队列研究发现，药物治疗胃食管反流病与患者较长的生存时间具有独立的相关性。[20]Lee JS, Ryu JH, Elicker BM , et al. Gastroesophageal reflux therapy is associated with longer survival time in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Am J Respir Crit Care Med. 2011;184:1390-1394.http://www.ncbi.nlm.nih.gov/pubmed/21700909?tool=bestpractice.com

IPF和GORD二者之间的关系尚未阐明。反流是否加重肺纤维化，使肺功能恶化仍不明确。

尽管给予最好的医疗，患者的病情仍然逐渐恶化，或者有药物治疗的禁忌证、严重的肺功能障碍、氧依赖和（或）恶化过程时，肺移植是一种可能的治疗选择。

肺移植的禁忌证包括严重的肺外疾病（例如肝、肾或心功能不全）或可能对生存产生消极影响的不稳定或不适当的心理状态/稳定性。许多医疗中心将申请肺移植患者的年龄限制在65岁以下，但是医疗中心越来越多地为选定的65岁及以上患者提供供体。[84]Kotloff RM, Thabut G. Lung transplantation. Am J Resp Crit Care Med. 2011;184:159-171.http://www.ncbi.nlm.nih.gov/pubmed/21471083?tool=bestpractice.com

依据指南，移植优先权决定于医疗急迫性和可能的预后。[85]Orens JB, Estenne M, Arcasoy S, et al. International guidelines for the selection of lung transplant candidates: 2006 update - a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006;25:745-755.http://www.ncbi.nlm.nih.gov/pubmed/16818116?tool=bestpractice.com

纳入等待移植名单的IPF患者病死率最高。[86]Thabut G, Mal H, Castier Y, et al. Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis. J Thorac Cardiovasc Surg. 2003;126:469-475.http://www.ncbi.nlm.nih.gov/pubmed/12928646?tool=bestpractice.com因此，应该对符合条件的肺移植患者进行早期评估，提高接受捐赠肺的机会。

尚不清楚单肺或双肺移植是否能提供生存获益，因为各种研究均存在矛盾的结果，而这个问题也被 ATS/ERS/JRS/ALAT 专家组延期至下一次指南更新。[58]Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis - an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192:e3-e19.https://www.thoracic.org/statements/resources/interstitial-lung-disease/IPF-Full-length.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26177183?tool=bestpractice.com[84]Kotloff RM, Thabut G. Lung transplantation. Am J Resp Crit Care Med. 2011;184:159-171.http://www.ncbi.nlm.nih.gov/pubmed/21471083?tool=bestpractice.com