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GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Diagnosis/testing. The diagnosis of familial pulmonary fibrosis is based on established clinical diagnostic criteria. Not all of the loci/genes associated with FPF are known. Mutations in SFTPC, TERT, and TERC have been identified in about 10% of individuals with familial pulmonary fibrosis and fewer than 1% of sporadic cases of idiopathic pulmonary fibrosis. Molecular genetic testing is available on a clinical basis; however, the predictive value of such tests is as yet unclear.
Management. Treatment of manifestations: Management of FPF and IIP is similar and depends on the type of IIP diagnosed in an individual; oxygen therapy may improve exercise tolerance in those with hypoxemia; lung transplantation may be considered, particularly in those who are unresponsive to therapy, have significant functional impairment, and have no other major illnesses that would preclude transplantation. Surveillance: The frequency of follow-up evaluations depends on the patient's individual diagnosis and status; those who are stable may be re-evaluated every three to six months, while others may need more frequent follow-up. Agents/circumstances to avoid: cigarette smoking. Testing of relatives at risk: every five years, in asymptomatic first-degree relatives (of individuals with FPF) over age 50 years: pulmonary function tests, HRCT images of the chest to detect early abnormalities, and standardized questionnaire to assess the presence of respiratory symptoms; up to 50% of unaffected at-risk family members have a positive screen (i.e., possibly have pulmonary fibrosis) and require further evaluation [a positive screen: at least class 2 dyspnea (breathlessness when hurrying on a level surface or walking up a slight hill), a DLCO below 80% of predicted, or presence of at least ILO category 1 findings on chest x-ray]. Other: Pharmacologic interventions have not been shown to alter the course of idiopathic pulmonary fibrosis (IPF).
Genetic counseling. The inheritance of familial pulmonary fibrosis is not clear. Autosomal dominant inheritance with reduced penetrance seems likely, though autosomal recessive inheritance cannot be ruled out. Prenatal diagnosis is available to families in which the TERT or TERC mutation has been identified; however, the predictive value of such tests is as yet unclear.
The diagnosis of an idiopathic interstitial pneumonia (IIP) is established by the presence of all of the following findings, based on criteria published as a consensus statement [King et al 2000, Travis et al 2002] and approved by the American Thoracic Society, the American College of Chest Physicians, and the European Respiratory Society:
A high-resolution computed tomography (HRCT) scan in the prone position (one 1.5-mm image every 2 cm from the apex to the base of the lungs) that demonstrates bibasilar reticular abnormalities with or without ground glass opacities
No significant exposure to environmental agents (e.g., asbestos, silica, metal dust, wood dust); no findings suggestive of hypersensitivity pneumonitis; no history of chronic infection or left ventricular failure; no evidence of collagen vascular disease (e.g., scleroderma or systemic lupus erythematosis); and no previous exposure to drugs associated with pulmonary fibrosis (e.g., bleomycin, methotrexate, cyclophosphamide, nitrofurantoin, anti-depressants) in an individual who is immunocompetent
Abnormal pulmonary function studies that include evidence of restriction (reduced VC with an increase in FEV1/FVC ratio) and/or impaired gas exchange (increased P(A-a)O2 with rest or exercise or decreasedf carbon monoxide diffusing capacity [DLCO])
Either of the following criteria:
A surgical lung biopsy that demonstrates a histologic pattern consistent with one of the forms of IIP (i.e., usual interstitial pneumonia, nonspecific interstitial pneumonia [NSIP], acute interstitial pneumonia, cryptogenic organizing pneumonia, respiratory bronchiolitis interstitial lung disease, or desquamative interstitial pneumonia) and cultures of the biopsies that are negative for bacteria, mycobacterium, and fungi
A transbronchial biopsy or bronchoalveolar lavage (BAL) that excludes alternative diagnoses
The presence of at least three of the following four criteria:
Age older than 50 years
Insidious onset of otherwise unexplained dyspnea on exertion
Duration of illness greater than or equal to three months
Bibasilar, inspiratory crackles (dry or "velcro"-type in quality)
The diagnosis of familial pulmonary fibrosis (FPF) is established in individuals with IIP who have at least one other first-degree relative (parent, sib, or offspring) with IIP.
GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Genes. Although the genes associated with familial pulmonary fibrosis (FPF) are not known, the following is known:
Mutations in TERT and TERC have recently been reported [Armanios et al 2007, Tsakiri et al 2007] in about 10% of individuals with FPF and fewer than 1% of sporadic cases of idiopathic PF. While these findings are promising and suggest that telomere length may play a role in the pathogenesis of IIP, further work is needed to identify the biologic importance of the mutations and the predictive (positive and negative) value of the sequence changes.
Mutations in the gene encoding surfactant protein C (SFTPC) are associated with the development of an inflammatory form of IIP in one family [Nogee et al 2001] and what appears to be both idiopathic pulmonary fibrosis (IPF) and NSIP in another large family [Thomas et al 2002]. In sporadic cases of IPF, surfactant protein C mutations appear to be rare [Lawson et al 2004].
In a Mexican cohort, mutations in the genes encoding surfactant protein A1 and surfactant protein B have been shown to be associated with IPF in nonsmoking and smoking populations, respectively [Selman et al 2003].
Polymorphisms of various cytokines (IL-1RA, TNF-alpha, and IL-6) have been reported to be associated with the development of IPF [Whyte et al 2000, Pantelidis et al 2001].
ELMOD2 was identified as a candidate gene for FPF in a genomic screen of six multiplex families from southeastern Finland [Hodgson et al 2006].
Loci. Loci associated with familial pulmonary fibrosis are not known. However, several loci have been associated with the development of familial sarcoidosis [Schurmann et al 2001].
The clinical symptoms, radiographic changes, pulmonary function testing abnormalities, and histopathologic findings of familial pulmonary fibrosis (FPF) are in need of further definition with little of this information known for familial cases as compared to sporadic cases. In a comparison of sporadic and familial IPF cases, individuals from families with FPF were found to have clinical, pathologic, and radiologic features similar to those of sporadic IPF cases [Lee et al 2005]. Families with FPF may, however, also exhibit multiple different IIP diagnoses (i.e., not just IPF) within a single family [Steele et al 2005]. Similar to sporadic cases, individuals with FPF usually present between age 50 and 70 years.
Like IPF, FPF may be complicated by lung cancer. Alveolar cell carcinoma, small cell carcinoma, and adenocarcinoma have been described [Beaumont et al 1981, McDonnell et al 1982].
Although fulminant interstitial lung disease (ILD) during infancy has been reported [Murphy & O'Sullivan 1981], it is likely that this early-onset ILD, also known as diffuse lung disease, is distinct pathogenically from adult-onset FPF.
No genotype-phenotype correlations are known.
Penetrance is unknown.
The prevalence of idiopathic pulmonary fibrosis is approximately 15:100,000 to 20:100,000 [Coultas et al 1994] and was recently estimated at 14:100,000 in the United States using a narrow case definition and data from a large health care claims database [Raghu et al 2006].
A descriptive report of 25 families with FPF suggests that familial cases account for 0.5%-2.2% of all individuals with IPF; therefore, the prevalence of FPF is 1.34:1,000,000 population [Marshall et al 2000].
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
Idiopathic pulmonary fibrosis (IPF) is an incurable disease with a five-year survival of 30%-50% from the time of diagnosis [King et al 2000]. Although progress has been made in understanding the molecular and cellular events involved in idiopathic pulmonary fibrosis, the exact pathogenesis has yet to be determined. The initiating stimulus is unknown in the majority of individuals, and only a subset of individuals (5%-20%) exposed to known fibrogenic agents actually develop PF.
Although familial pulmonary fibrosis (FPF) is rare, its overlap with IPF makes studies of FPF kindreds important because they may provide insights into the etiology and pathogenesis of IPF. Several lines of evidence suggest that inherited genetic factors play a role in the development of pulmonary fibrosis, at least in a subset of individuals. The role of genetic factors in the development of PF is supported by the occurrence of forms of pulmonary fibrosis that appear to be inherited (familial pulmonary fibrosis and pulmonary fibrosis associated with pleiotropic genetic disorders), the apparent variation in individual susceptibility to fibrogenic dusts that are known to cause pulmonary fibrosis, and the differences in development of pulmonary fibrosis observed between inbred strains of mice following experimental exposure to fibrogenic agents.
Interstitial lung disease is observed as a manifestation of a number of genetic disorders. Although these genetic disorders are distinct clinically and pathologically, they are all associated with PF, pointing toward a genetic basis influencing this association.
The following are other inherited diffuse parenchymal lung diseases:
Hermansky-Pudlak syndrome [Depinho & Kaplan 1985]. Hermansky-Pudlak syndrome (HPS) is a multisystem disorder characterized by tyrosinase-positive oculocutaneous albinism, a bleeding diathesis resulting from a platelet storage pool deficiency, and, in some cases, pulmonary fibrosis or granulomatous colitis. Pulmonary fibrosis typically causes symptoms in the early thirties and progresses to death within a decade. Hermansky-Pudlak syndrome is known to be associated with a defect in five-hydroxytryptamine [Gerritsen et al 1977] and lysosomal metabolism [Schinella et al 1980]. In Hermansky-Pudlak syndrome, the release of PDGF-B by alveolar macrophages is enhanced [Witkop et al 1989, Harmon et al 1994]. This growth factor is thought to play a pathogenic role in idiopathic pulmonary fibrosis [Martinet et al 1987, Antoniades et al 1990, Nagaoka et al 1990, Shaw et al 1991]. Inheritance is autosomal recessive. Seven genes are known to cause HPS: HPS1, HPS3, HPS4, HPS5, HPS6, AP3B1, and DTNBP1.
Neurofibromatosis type 1 (NF1) [Riccardi 1981] is characterized by multiple café au lait spots, axillary and inguinal freckling, multiple discrete dermal neurofibromas, and iris Lisch nodules. Learning disabilities are common. Less common but potentially more serious manifestations include plexiform neurofibromas, optic and other central nervous system gliomas, malignant peripheral nerve sheath tumors, osseous lesions, and vasculopathy.
Pulmonary fibrosis is an occasional finding, though the association of pulmonary fibrosis with NF1 is somewhat controversial today [Ryu et al 2005]. The symptomatic onset of lung disease, whenit occurs, is usually between age 35 and 60 years, although symptomatic pulmonary fibrosis has developed as early as the second decade. Dyspnea is the usual presenting symptom. Pulmonary function tests show restrictive or obstructive lung defect with a reduced carbon monoxide diffusing capacity (DLCO). The natural history of interstitial lung disease in NF1 is unclear. Progression to respiratory failure, pulmonary hypertension, and cor pulmonale may occur. No effective treatment is known. Like IPF, the interstitial lung disease in NF1 is sometimes complicated by scar carcinoma.
Radiographic findings include diffuse interstitial pulmonary fibrosis and bullae. The bullae are usually apical, may appear with or without fibrosis, and are often large. A chest roentgenogram early in the course of the disease may show patchy airspace disease and may even be normal despite interstitial pulmonary fibrosis documented by lung biopsy. Pleural disease and mediastinal adenopathy are not a known feature of this disease, although neurofibromas can sometimes simulate pleural thickening or a mediastinal mass.
The pathologic features of interstitial lung disease in NF1 are nonspecific. Since these were described prior to the currently evolved understanding of specific histologic subgroups, it is unclear if the fibrotic pattern is unclassifiable or represents one of the precisely defined histologic subgroups.
Other thoracic radiographic manifestations are caused by the direct effect of neurofibromas. Intrathoracic meningomyeloceles may present as a posterior mediastinal mass. 'Twisted ribbon' rib deformities caused by the pressure of intercostal fibromas, vertebral defects, and scoliosis have been described. Inheritance is autosomal dominant.
Tuberous sclerosis complex (TSC) [Harris et al 1969, Malik et al 1970] involves abnormalities of the skin (hypomelanotic macules, facial angiofibromas, shagreen patches, fibrous facial plaques, ungual fibromas), brain (cortical tubers, subependymal nodules, seizures, mental retardation/developmental delay), kidney (angiomyolipomas, cysts), and heart (rhabdomyomas, arrhythmias). Pulmonary lymphangioleiomyomatosis (LAM) occurs in a small proportion of premenopausal women with TSC. Individuals with LAM typically present with symptoms of dyspnea on exertion and progressive loss of lung function that may resemble some of the presenting symptoms of FPF.
The diagnosis of TSC is based on clinical findings. Two causative genes, TSC1 and TSC2, have been identified. Two-thirds of affected individuals have TSC as the result of a de novo gene mutation. Inheritance is autosomal dominant.
Neimann-Pick disease type B [Terry et al 1954] is a lipid storage disease characterized by the accumulation of sphingomyelin in the central nervous system and the reticuloendothelial system. It can present in infants, children, or adults. Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs, whereas children and adults present with neurologic findings of ataxia, gaze palsy, dementia, dystonia, and seizures.
The incidence of lung involvement is unknown. Chest radiography may show a reticulonodular or miliary pattern; progression to honeycombing has been described. Reticuloendothelial cells filled with sphingomyelin may fill the alveolar spaces and interstitium and can be recovered with bronchoalveolar lavage. No effective treatment is known.
Niemann-Pick disease type B is caused by mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1). Inheritance is autosomal recessive. (See Acid Sphingomyelinase Deficiency.)
Gaucher disease [Schneider et al 1977] encompasses a continuum of five clinical subtypes that range from a perinatal-lethal form to an asymptomatic form. The pulmonary manifestations of Gaucher disease type 1 are caused by Gaucher cells infiltrating the interstitium, filling the alveoli or obstructing pulmonary capillaries. Obliteration of pulmonary capillaries may result in pulmonary hypertension and cor pulmonale. Acute fatal bone marrow embolization of Gaucher cells to the lungs has been described. Pulmonary infections occur with increased frequency.
Histopathologic examination shows Gaucher cell infiltration, but inflammation and fibrosis are not usual features. The Gaucher cells stain positively with PAS and autofluoresce. Gaucher cells may be found in the sputum or in the bronchial washes. Chest radiographic findings are not specific. Diffuse interstitial infiltrates that occasionally have a miliary appearance have been described, as has mediastinal adenopathy. Pulmonary function tests reveal typical restrictive lung defect with a reduced DLCO.
The diagnosis of Gaucher disease relies on demonstration of deficient glucosylceramidase enzyme activity in peripheral blood leukocytes or other nucleated cells. Molecular genetic testing of the causative gene GBA is available in clinical laboratories. Inheritance is autosomal recessive.
Familial hypocalciuric hypercalcemia [Auwerx et al 1985] is a very rare disorder characterized by hypocalciuric hypercalcemia, interstitial lung disease (ILD) / pulmonary fibrosis, and recurrent respiratory tract infections caused by granulocyte dysfunction associated with a relative deficiency in myeloperoxidase [Auwerx et al 1985]. The disease usually presents in the fourth decade. Reticulonodular infiltrates that may progress to honeycombing on chest radiograph and restrictive pulmonary physiology are typical findings. Disease progression appears to be slow with survival after diagnosis being about ten years. The disease is probably inherited in an autosomal dominant manner. Support for this mode of inheritance comes from one family with three sibs clinically affected by ILD. In this relatively large family, 45% of 38 family members studied had a reduced DLCO, suggesting subclinical disease. Several asymptomatic individuals also had abnormalities of BAL fluid cell count, suggesting active alveolitis. In addition, 60% had recurrent respiratory tract infections. The disorder is caused by mutation in CASR, encoding the calcium-sensing receptor.
To establish the extent of disease in an individual diagnosed with idiopathic interstitial pneumonia (IIP), the following evaluations are recommended:
Clinical history
Chest radiograph
Pulmonary function studies
In cases that could represent a form of IIP:
High-resolution computed tomography scan
To establish a definite diagnosis of IIP:
Lung biopsy
The management of the individual with familial pulmonary fibrosis (FPF) is similar to that for IIP and dependent upon the type of IIP diagnosed for each individual within the family [King et al 2000, Travis et al 2002].
Lung transplantation may be a consideration in selected individuals with FPF. In general, those who are unresponsive to therapy, have significant functional impairment, and have no other major illnesses that would preclude transplantation are good candidates.
Oxygen therapy may improve exercise tolerance in patients with hypoxemia.
The frequency of follow-up evaluations for persons with FPF depends largely on the patient's individual diagnosis and status. Those who are stable may be evaluated every three to six months, while others may need more frequent follow-up.
Cigarette smoking places individuals at increased risk of developing idiopathic pulmonary fibrosis (IPF) and FPF as well [Steele et al 2005].
Every five years, asymptomatic first-degree relatives (of individuals with FPF) older than age 50 years should undergo pulmonary function tests, obtain HRCT images of the chest to detect early abnormalities, and complete a standardized questionnaire to assess the presence of respiratory symptoms. Family members are considered to have a positive screening evaluation (i.e., to possibly have pulmonary fibrosis) if they have at least class 2 dyspnea (breathlessness when hurrying on a level surface or walking up a slight hill), a DLCO below 80% of predicted, or presence of at least ILO category 1 findings on chest x-ray [International Labor Office 1980]. In previous studies, these simple screening tests have been found to be sensitive for diagnosis [Watters et al 1986, Hartley et al 1994] and prognosis of pulmonary fibrosis [Watters et al 1986, Schwartz et al 1994a, Schwartz et al 1994b]. Up to 50% of unaffected at-risk family members have a positive screen and require further evaluation.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Antifibrotic agents such as interferon gamma and perfenidone are currently being tested to determine their efficacy in treating IPF. If found to be effective in IPF, these agents may also be effective in FPF.
Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.
Pharmacologic interventions have not been shown to alter the course of IPF.
Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These organizations have been established for individuals and families to provide information, support, and contact with other affected individuals.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
The inheritance of familial pulmonary fibrosis (FPF) is not clear. Family studies are most consistent with autosomal dominant inheritance with reduced penetrance. At least three studies on FPF, including one family with 16 affected individuals [Bonanni et al 1965], support an autosomal dominant mode of inheritance with reduced penetrance. The study by Marshall et al [2000] investigating 25 families with FPF also supports this model but cannot exclude autosomal recessive inheritance.
Parents of a proband
Most individuals diagnosed with FPF have an affected parent.
Although most individuals diagnosed with FPF have an affected parent, the disorder may appear to have skipped a generation (i.e., the individual diagnosed has an affected grandparent) because of reduced penetrance.
Sibs of a proband
The risk to the sibs of the proband depends upon the genetic status of the proband's parents.
If a parent of the proband is affected or known to have a disease-causing mutation on the basis of family history, the risk to the sibs of inheriting the mutation is 50%. Because the penetrance is likely reduced, the risk to sibs of being affected is less than 50%.
Offspring of a proband. Each child of an individual with FPF has a 50% chance of inheriting the disorder; however, because penetrance is likely reduced in FPF, the risk to offspring of being affected is less than 50%.
Other family members of a proband. The risk to other family members depends upon the status of the proband's parents. If a parent is found to be affected, his or her family members are at risk.
Other modes of inheritance. Autosomal recessive inheritance may need to be considered in simplex cases (i.e., cases with only one affected individual in a family) and in families with only affected sibs [Marshall et al 2000].
Family planning. The optimal time for determination of genetic risk is before pregnancy. It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.
DNA banking. DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant when the gene(s) in which disease-causing mutations occur has/have not been identified. See
for a list of laboratories offering DNA banking.
Prenatal testing for TERT or TERC mutations is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at approximately 15-18 weeks’ gestation or chorionic villus sampling (CVS) at approximately ten to 12 weeks’ gestation. However, a TERT or TERC mutation must be identified in the family (by testing an affected family member) before prenatal testing can be performed. The predictive value of such tests is as yet unclear.
Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.
Requests for prenatal diagnosis of adult-onset diseases are difficult situations requiring genetic counseling. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although decisions about prenatal testing are the choice of the parents, discussion of these issues is appropriate.
Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.
| Gene Symbol | Chromosomal Locus | Protein Name | Locus Specific | HGMD |
|---|---|---|---|---|
| TERC | 3q21-q28 | Unknown | Telomerase Database TR mutations | TERC |
| TERT | 5p15.3 | Telomerase reverse transcriptase | Telomerase Database TERT mutations | TERT |
| 178500 | PULMONARY FIBROSIS, IDIOPATHIC |
| 187270 | TELOMERASE REVERSE TRANSCRIPTASE; TERT |
| 602322 | TELOMERASE RNA COMPONENT; TERC |
Not all of the loci/genes associated with familial pulmonary fibrosis are known.
See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These organizations have been established for individuals and families to provide information, support, and contact with other affected individuals. GeneTests provides information about selected organizations and resources for the benefit of the reader; GeneTests is not responsible for information provided by other organizations.—ED.
Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed Clinical Queries page.
No specific guidelines regarding genetic testing for this disorder have been developed.
David Schwartz was educated at the University of Rochester (BA) and the University of California at San Diego (MD). Following a residency and chief residency in Internal Medicine at Boston City Hospital, he completed a fellowship in Occupational Medicine at the Harvard School of Public Health, where he received an MPH, and a Pulmonary and Critical Care Fellowship at the University of Washington in Seattle. In addition, while at the University of Washington, he completed a research fellowship in the Robert Wood Johnson Clinical Scholars Program. Dr. Schwartz was a faculty member at the University of Iowa for 12 years where he completed a sabbatical in molecular genetics with Dr. Jeff Murray. He joined Duke University in 2000, where he served as a Professor of Medicine and Genetics, Director of the Division of Pulmonary and Critical Care Medicine, and Director of the Program in Environmental Genomics. Dr. Schwartz was funded to establish three NIH Centers at Duke: a Center focusing on Environmental Genomics, a Program Project in Environmental Asthma, and an Environmental Health Sciences Research Center. He has served on several study sections and editorial boards, is a member of the American Society for Clinical Investigation and the Association of American Physicians, and was awarded the Scientific Accomplishment Award from the American Thoracic Society in 2003. In May 2005, he became the Director of the National Institute of Environmental Health Sciences (NIEHS) at the NIH and the National Toxicology Program.
5 February 2009 (cd) Revision: prenatal testing for TERT and TERC mutations available clinically
2 October 2007 (cd) Revision: mutations in TERT and TERC reported to "increase susceptibility to adult-onset IPF" [Armanios et al 2007, Tsakiri et al 2007]; molecular testing for TERT and TERC mutations available on a clinical basis but the predictive value of the tests is as yet unclear.
11 June 2007 (me) Comprehensive update posted to live Web site
21 January 2005 (me) Review posted to live Web site
8 April 2004 (ds) Original submission
