New Idiopathic Pulmonary Fibrosis (IPF) Treatment Guideline issued

Hopefully these new treatment guidelines will help in the diagnosis and treatment of IPF. When I was diagnosed with IPF in 1999 I was given two inhalers consisting of a bronchodilator and an anti-inflamatory. I was also put on daily doses of 50 mg of prednisone, plus azathioprine. The Azathoprine (Imuran) caused an allergic reaction so they switched me to Cyclophosphamide (Cytoxan) which I could not tolerate because of side effects (edema). None of these therapies slowed the progression of my disease but the inhalers did alleviate the coughing.

Medscape Pulmonary Medicine

March 26, 2011 — The American Thoracic Society (ATS) has issued new official clinical guidelines on the diagnosis and management of idiopathic pulmonary fibrosis (IPF) and published this Joint Statement in the March 15 issue of the American Journal of Respiratory and Critical Care Medicine. In addition to summarizing current evidence regarding the epidemiology, cause, diagnosis, and management of IPF, the new recommendations discuss available therapeutic options, including pharmacologic and nonpharmacologic treatments and palliative care.

"In the decade since the publication of the previous statement on IPF, studies have used the criteria for the diagnosis of IPF and recommendations published in the previous consensus-based statement to further our understanding of the clinical manifestations and course of IPF, and there has been an increasing body of evidence pertinent to its clinical management," said committee chair Ganesh Raghu, MD, director of the Interstitial Lung Disease/Sarcoid/Pulmonary Fibrosis Program at the University of Washington Medical Center in Seattle, in a news release. "The accumulated data and observations made in these studies are substantial and have allowed us to provide new guidelines for the diagnosis and management of IPF to the global pulmonary community-at-large to the patients and to all concerned based on evidence for the very first time."

A Progressive, Fatal Disease

IPF is a chronic, progressive, fatal form of fibrotic lung disease affecting mostly relatively older adults, with a clinical presentation of shortness of breath during exertion. Although the cause of IPF is unclear, a subgroup of patients with IPF has a genetic predisposition. Injury to the lungs triggered by still-undetermined factors causes formation of scar tissue, leading to lung tissue thickening, stiffness, and fibrosis. During the course of several years, IPF may be slowly progressive with sporadic episodes of acute respiratory worsening.

The ATS collaborated with the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association to develop the Joint Statement, which updates and replaces ATS guidelines published in 2000. All available evidence was reviewed by selected experts from each of these organizations and was ranked from weak to strong on the basis of clinical relevance. The statement has also been formally endorsed by the Society of Thoracic Radiology and by the Pulmonary Pathology Society.

"The objective of these guidelines is to systematically and carefully analyze all evidence accumulated since the publication of the 2000 consensus statement and to provide evidence-based recommendations for management, with an emphasis on diagnosis and treatment," Dr. Raghu said. "The methodology used and the strength of the recommendations are all very transparent, and thus the clinician confronted with the patient with IPF is empowered for the very first time to make the most appropriate decisions tailored to individual patient's values and preferences, and to make appropriate decisions regarding all aspects of disease management."

"For example, in the case of a weak recommendation, clinicians are especially required to spend adequate time with patients to discuss patients' values and preferences," Dr. Raghu said. "This may lead a significant proportion of patients to choose an alternative approach."

Diagnosis

Diagnosis of IPF requires exclusion of known causes of interstitial lung disease such as domestic and occupational/environmental lung exposures, connective tissue disease, and drug toxicity. Diagnosis also requires the presence of a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) scan in patients in whom surgical lung biopsy is not indicated.

Chest radiography is not as useful as HRCT in evaluating patients with suspected IPF, and transbronchial biopsy should not be used for suspected IPF in the majority of patients. Serologic testing should be performed in the majority of patients suspected of having IPF.

Available Treatments

Clinical treatment of all patients with IPF should include ample discussion of the patients' views regarding treatment and availability of clinical trials for which they may be appropriate candidates. Advanced directives must also be discussed in the ambulatory setting.

Oxygen supplementation is strongly recommended for patients with hypoxemia, whereas pulmonary rehabilitation is a weak recommendation.

At 4 to 6 months, or sooner as clinically indicated, all patients should be reevaluated to identify complications and to monitor for disease progression.

Pharmacotherapy should only be considered for a carefully selected, limited number of patients who are willing to accept potential treatment risks, even if anticipated benefits are small. For acute exacerbation, corticosteroids are weakly recommended as an appropriate treatment option.

Most patients with IPF should not be treated with combination corticosteroid, azathioprine, and acetylcysteine therapy, or with acetylcysteine monotherapy, but either of these treatments may be appropriate for a minority of patients (weak recommendation). Similarly, there are also weak recommendations that the majority of patients with IPF should not be treated with anticoagulants or with pirfenidone, but either of these treatments may be reasonable for a minority of patients.

Sildenafil is an oral phosphodiesterase 5 inhibitor that has been shown to safely lower pulmonary vascular pressures in patients with IPF. Small studies in patients with IPF and pulmonary hypertension have shown better walk distance and pulmonary hemodynamics associated with sildenafil treatment for 8 to 12 weeks. One phase 3, randomized controlled trial of sildenafil showed no difference in the primary endpoint of 6-minute-walk distance, but there were statistically significant differences in the change in dyspnea, PaO2, diffusing capacity for carbon monoxide, and quality of life favoring sildenafil. However, a second randomized study showed no significant difference.

For most patients with respiratory failure caused by disease progression, mechanical ventilation is not recommended, but this is a weak recommendation.

For highly selected patients at increased risk for mortality, lung transplantation is a feasible therapeutic option.

The goal of palliative care is to alleviate cough, shortness of breath, and other symptoms and to provide comfort, rather than to address the cause or progression of fibrosis.

Genetic Studies and Other Research Possible

The Joint Statement also offers suggestions for future research, including genetic studies. Successful treatment of IPF may require a combination of therapies targeting multiple pathways involved in fibroproliferation.

"It is hoped that with continued collaboration between basic and clinical scientists, the goals of finding the cause or causes of IPF, detecting disease in preclinical and early stages by appropriate biomarkers, genetic predisposition and/or other host susceptibility factors, improving outcomes and quality of life, prolonging survival and, ultimately, curing IPF will be realized," Dr. Raghu said.

Stem cell transplant research, gene therapy, and other preventive and regenerative strategies appear to be promising and should be aggressively tested in clinical trials using sophisticated study design, endpoints of proven clinical value, and statistical methodology.

"While this evidence-based guidelines for clinical management of IPF are prudent for better management of patients with IPF in 2011 and immediate future, this guideline does not address the optimal endpoints besides survival that need to be assessed in future clinical trials for IPF," Dr. Raghu said. "Ideally, a consensus among experts in the regulating agencies and experienced investigators in clinical trials of IPF will lead to design of better clinical trials that are feasible and result in improved survival, quality of life and other outcomes that are clinically significant for patients with IPF. The new diagnostic criteria provided in this new guideline will greatly enhance the accuracy of the diagnosis of IPF and facilitate enrollment of patients with well and better defined IPF in future studies and thus make more progress than the preceding decade."

A complete description of various financial relationships of the joint statement writing committee is available in the original article.

Am J Respir Crit Care Med. 2011;183:788-824. Abstract