Goal 2: Reduce Human Disease

Nontuberculous mycobacterial (NTM) lung infections

The true prevalence of Nontuberculous mycobacterial (NTM) lung infections remains incompletely understood, however several aspects of NTM lung disease prevalence are becoming more clear. NTM lung disease is currently more common in the U.S. than TB (by a factor of 3) and has consistently been shown to be increasing in prevalence. When viewed in the context of likely universal environmental NTM exposure this increasing ...more »

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NTM lung disease is most common among older and female patients with estimated prevalences as high as 50-60 cases per 100,000 in this group and can be seen in this context as a women’s health issue.  While it may appear paradoxical, NTM lung disease studies would both profoundly change outcomes for a relatively rare condition overall, but would also benefit, in a potentially profound way, a large number of patients in a selected population (older female patients) in which the disease is not so rare.   To date there has been no significant funding for any aspect of NTM lung disease outside of limited support from the pharmaceutical industry.  The studies that have been done to date are largely single center/institution studies with relatively small numbers of patients.  Again, the few collaborative studies that have been done were accomplished with support from the pharmaceutical industry.  NTM lung diseases, and associated lung diseases such as bronchiectasis have not attracted the interest or support of major non-industry funding sources.

Feasibility and challenges of addressing this CQ or CC :

Essentially every aspect of Nontuberculous Mycobacterial (NTM) lung disease is associated with some level of controversy. The diagnostic guidelines were adopted primarily as a result of experience with common NTM pathogens such as Mycobacterium avium complex (MAC), M. kansasii , and M. abscessus. The relevance of the diagnostic guidelines for other potential NTM pathogens, especially rarely encountered organisms (in the U.S.) such as M. xenopi and organisms usually associated with specimen contamination such as M. fortuitum , is untested and unknown. The treatment of NTM lung disease is almost entirely based on case series, both retrospective and prospective, with consensus on basic treatment concepts. Treatment outcomes remain unsatisfactory for many pathogens including the most common, MAC, and prospective treatment trials are needed to establish not just optimal treatment regimens but the roles of agents in common use, such as clofazimine, the fluoroquinolones and inhaled amikacin, of unproven value.  Other basic studies including radiographic and pulmonary function evolution for treated and untreated disease and long term natural history of treated and untreated NTM lung disease patients are lacking.

Name of idea submitter and other team members who worked on this idea : American Thoracic Society member

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Goal 2: Reduce Human Disease

Therapy for lung infections

1. Monotherapy with a quinolone vs combination therapy with a 3rd generation cephalosporin. The issue of the best antibiotic treatment for severe CAP has been a major area of contention now for a decade and it is the most common cause of infectious death in the United States. 2. Combination therapy vs monotherapy for pneumonia due to Pseudomonas. This is another major area of contention – for nearly 2 decades, and generates ...more »

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Name of idea submitter and other team members who worked on this idea : American Thoracic Society member

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Goal 2: Reduce Human Disease

Interstitial Lung Disease

Is FVC a valid surrogate for mortality in patients with idiopathic pulmonary disease?

Submitted by (@nhlbiforumadministrator)

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This question is central to all future clinical research in the field and MUST be answered in the context of an interventional clinical trial. Longitudinal cohort studies correlating FVC change with survival are insufficient. The intervention that would make the most sense to test currently is pirfenidone. It is approved for use in many countries and many experts (including the submitter of this compelling question) believe it is likely effective. A mortality-driven clinical trial of pirfenidone vs. placebo would address this question directly, as well as determine the true impact of pirfenidone on clinically meaningful endpoints.

Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Interstitial Lung Disease

Does prednisone therapy improve outcomes in acute exacerbation of IPF?

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It is common practice to give high-dose prednisone to patients experiencing acute exacerbation of IPF, a relatively common (10-15% annual risk) and deadly event, but there are no good data to support its use. There is a significant risk of morbidity from this therapy. A well-designed multicenter trial could answer this question definitively.

Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Interstitial Lung Disease

Do the non-pharmacological interventions of pulmonary rehabilitation and supplemental oxygen for exertional hypoxemia improve quality of life and functional status in patients with chronic fibrotic ILD?

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Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

There is good evidence from small controlled trials that pulmonary rehabilitation improves walk distance and shortness of breath in patients with chronic ILD. Both pulmonary rehabilitation and supplemental oxygen are commonly recommended to these patients at great cost. A randomized clinical trial using factorial design could address the impact of these two therapies individually as well as together on clinically meaningful outcomes.

Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Childhood Interstitial Lung Disease

What is the natural history of the best characterized ChILD disorders (surfactantrelated sequence variants, neuroendocrine cell hyperplasia of infancy (NEHI),pulmonary interstitial glycogenosis (PIG),idiopathic pulmonary hemosiderosis)?

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We know little about the natural history of many of the child entities, and their relative rarity makes it difficult for any one center to answer the major questions they pose. The children has begun a patient registry that will begin to address the issue of natural history and disease tracking.

 

a. To improve the power of such a registry, we suggest that support be provided to find novel methods to link this data base to available electronic medical records of participating centers in order to assess physiologic and other clinical associations with specific diseases.

 

b. Support for a biomarker repository holding serum, frozen and fixed lung tissue, patient DNA, RNA, and proteomic and metabolomic materials, and bronchoalveolar lavage effluent and cell pellets, will allow for genome wide analysis as well as proteomic and metabolomic analysis.

Feasibility and challenges of addressing this CQ or CC :

This question is best addressed in the context of a multicenter data registry, ideally linked to a clinical sample.

Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Childhood Interstitial Lung Disease

What is the relationship of ChILD disorders to adult diffuse lung disease?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

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This would need to be addressed in the context of databases such as those for familial idiopathic pulmonary fibrosis (F-IPF) or IPF clinical trials, as well as perhaps databases for COPD and pulmonary hypertension. What is the prevalence and spectrum of childhood respiratory disease in family members within these cohorts? What is the prevalence of adult lung disease in family members in ChILD registries? In disorders such as surfactant-related sequence variants, which can cause disease across the lifespan, what are likely “2nd hits”, genomic or environmental, that may lead to clinical disease at particular ages/developmental stages?

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Goal 2: Reduce Human Disease

Childhood Interstitial Lung Disease

What is the relationship of ChILD disorders to more common childhood respiratory diseases?

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For example, what is the role of surfactant-related sequence variants in chronic lung disease of prematurity? Cystic fibrosis? Severe bronchiolitis? Refractory asthma?

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Goal 2: Reduce Human Disease

Childhood Interstitial Lung Disease

What is the relationship of ChILD disorders to other clinical populations that manifest ILD?

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ILD is a prominent feature of systemic inflammatory diseases, such as lupus. ILD is also among the most common long-term complications of therapy for childhood cancer. What is the relationship of surfactant-related sequence variants to expression of clinical ILD in these cohorts?

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Goal 2: Reduce Human Disease

Lung Transplantation

As in other solid organ transplants, adherence to the medical regimen after adult and pediatric lung transplantation is less than ideal and contributes to poor health outcomes. a) How can we improve the prediction of which lung transplant recipients are at greatest risk for nonadherence? b) What are the most efficient and effective ways of assessing nonadherence in the clinical setting? c) Conduct clinical trials of ...more »

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Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Lung Transplantation

Although the majority of lung recipients experience significant health improvement, they also frequently face serious symptom distress, impaired physical functioning and poor quality of life due to post-transplant morbidity, such as chronic rejection, infection and multiple side-effects of immunosuppression. a) Conduct clinical trials of interventions designed to maximize clinicians' support of patients' self-management ...more »

Submitted by (@nhlbiforumadministrator)

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a) Conduct clinical trials of interventions designed to maximize clinicians' support of patients' self-management behaviors so that patients and clinicians working together can achieve optimal control of disease, reduce symptom distress and complications, and promote quality of life.

 

b) Evaluate the impact of integrating palliative care and transplant care for symptom management, goal setting and advanced care planning along the entire lung transplant illness trajectory (pre, post and end of life).

Name of idea submitter and other team members who worked on this idea : ATS Member

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