Neurofibromatosis-associated lung disease: A case series and literature review

Department of Medicine, University of California, San Francisco, San Francisco, California, United States
European Respiratory Journal (Impact Factor: 7.64). 02/2007; 29(1):210-4. DOI: 10.1183/09031936.06.00044006
Source: PubMed


An association of neurofibromatosis with diffuse lung disease (NF-DLD) has been described, but its true prevalence and characteristics remain unclear. The objective of the present study was to define diffuse lung disease in patients with neurofibromatosis. A retrospective case series and literature review in a tertiary care academic medical centre is reported in which medical records, chest radiographs and high-resolution computed tomography (HRCT) scans were reviewed. A total of 55 adult patients with neurofibromatosis were identified, three of whom had NF-DLD. A literature review revealed 16 articles reporting 61 additional cases, yielding a total of 64 NF-DLD cases. The mean age of patients was 50 yrs. Males outnumbered females; most reported dyspnoea. Of the 16 subjects with documented smoking histories, 12 were ever-smokers. Eight patients had HRCT scan results demonstrating ground-glass opacities (37%), bibasilar reticular opacities (50%), bullae (50%), cysts (25%) and emphysema (25%); none had honeycombing. A group of 14 patients had surgical biopsy results that showed findings of interstitial fibrosis (100%) and interstitial inflammation (93%). In conclusion, neurofibromatosis with diffuse lung disease is a definable clinical entity, characterised by upper lobe cystic and bullous disease and lower lobe fibrosis. Its relationship to smoking remains unclear.

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    • "She reported no history of environmental or occupational exposure to other potential carcinogens for lung cancer. However, as part of her thorough followup, she underwent a low-dose HRCT of the lungs to investigate any occult interstitial lung abnormalities and presence of lung cysts that have been described in neurofibromatosis patients [1]. HRCT of the lungs detected an incidental ill-defined solitary pulmonary nodule 1.4 cm in diameter, exhibiting a ground-glass opacity and air alveologram (Figure 2). "
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    ABSTRACT: Lung cancer associated with neurofibromatosis type I is considered very rare, and only a few case reports have been described in the literature. There is some evidence that a genetic linkage between neurofibromatosis and carcinogenesis in the lung may exist. We present a 42-year-old female, lifetime nonsmoker with a known history of neurofibromatosis type I, free of respiratory symptoms, who underwent a low-dose HRCT of the lungs to investigate any occult interstitial lung changes. A solitary ill-defined nodule of a ground-glass opacity was detected incidentally in the middle lobe with no associated lymphadenopathy or metastatic disease. Several thin-walled lung cysts were also seen in the lower lobes. Histological analysis of the nodule after middle lobectomy revealed well-differentiated adenocarcinoma. The patient did not receive systemic chemotherapy or radiotherapy. She was free of disease on 18-month followup.
    Full-text · Article · Feb 2013
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    • "With regard to non-neoplastic diseases, the 2-fold excess for obstructive chronic bronchitis among persons 40 years of age and older is consistent with the well-known respiratory manifestations of NF1. In NF1, the thorax and lungs can be affected in several ways, given the dense distribution of peripheral nerves throughout the thorax: cutaneous and subcutaneous neurofibromas on the chest wall and chest wall deformities; kyphoscoliosis; ribbon deformity of the ribs; thoracic neoplasms; parenchymal neurogenetic tumors [29-31]; and other respiratory manifestations that severely impair pulmonary function, such as upper airway obstruction by neurofibromas, central hypoventilation, diaphragm paralysis, diffuse and interstitial lung disease, and primary pulmonary hypertension [32-35]. "
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    ABSTRACT: Persons affected by neurofibromatosis type 1 (NF1) have a decreased survival, yet information on NF1-associated mortality is limited. METHODS/AIM: The National Mortality Database and individual Multiple-Causes-of-Death records were used to estimate NF1-associated mortality in Italy in the period 1995-2006, to compare the distribution of age at death (as a proxy of survival) to that of the general population and to evaluate the relation between NF1 and other medical conditions by determining whether the distribution of underlying causes of NF1-associated deaths differs from that of general population. Of the nearly 6.75 million deaths in the study period, 632 had a diagnosis of NF1, yet for nearly three-fourths of them the underlying cause was not coded as neurofibromatosis. The age distribution showed that NF1-associated deaths also occurred among the elderly, though mortality in early ages was high. The mean age for NF1-associated death was approximately 20 years lower than that for the general population. The gender differential may suggest that women are affected by more severe NF1-related complications, or they may simply reflect a greater tendency for NF1 to be reported on the death certificates of young women. Regarding the relation with other medical conditions, we found an excess, as the underlying cause of death, for malignant neoplasm of connective and other soft tissue and brain, but not for other sites. We also found an excess for obstructive chronic bronchitis and musculoskeletal system diseases among elderly persons. This is the first nationally representative population-based study on NF1-associated mortality in Italy. It stresses the importance of the Multiple-Causes-of-Death Database in providing a more complete picture of mortality for conditions that are frequently not recorded as the underlying cause of death, or to study complex chronic diseases or diseases that have no specific International Classification of Diseases code, such as NF1. It also highlights the usefulness of already available data when a surveillance system is not fully operational.
    Full-text · Article · Mar 2011 · Orphanet Journal of Rare Diseases
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    • "Primary biliary cirrhosis and chronic hepatitis have also been reported to be associated with parenchymal lung dysfunction [137,138]. In addition, there are reports on ILD in association with neurocutaneous disorders (tuberous sclerosis, neurofibromatosis, ataxia-telangiectasia) and amyloidosis [139]. "
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    ABSTRACT: Interstitial lung disease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1) exposure-related ILD; 2) systemic disease-associated ILD; 3) alveolar structure disorder-associated ILD; and 4) ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.
    Full-text · Article · Aug 2010 · Orphanet Journal of Rare Diseases
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