Interstitial lung disease in patients with ataxia‐telangiectasia

Schroeder, Scott A.; Swift, Michael; Sandoval, Claudio; Langston, Claire

doi:10.1002/ppul.20209

Cited by 76 publications

(77 citation statements)

References 20 publications

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“…Declining lung function in A-T may be associated with oropharyngeal dysphasia and aspiration, recurrent pneumonias and bronchiectasis, chemotherapy, and interstitial lung disease. [16][17][18] Detection of poor lung function or rapidly declining lung function can help with the recognition of a condition that may be amenable to clinical intervention. Although spirometry alone can be useful in tracking declines in lung function, FVC predicted values in A-T are often low.…”

Section: Discussionmentioning

confidence: 99%

“…Interstitial lung disease has also been reported in the absence of recognized infections. 6 Although, the etiology of interstitial lung disease has not been elucidated treatments have included the use of corticosteroids. Individuals with A-T are also more vulnerable to the development of significant pulmonary complications from chemotherapy used to treat malignancies.…”

Section: Introductionmentioning

confidence: 99%

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Pulmonary function in adolescents with ataxia telangiectasia

McGrath‐Morrow¹,

Lefton‐Greif²,

Rosquist³

et al. 2007

Pediatric Pulmonology

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Summary. Introduction. Pulmonary complications are common in adolescents with ataxia telangiectasia (A-T), however objective measurements of lung function may be difficult to obtain because of underlying bulbar weakness, tremors, and difficulty coordinating voluntary respiratory maneuvers. To increase the reliability of pulmonary testing, minor adjustments were made to stabilize the head and to minimize leaks in the system. Fifteen A-T adolescents completed lung volume measurements by helium dilution. To assess for reproducibility of spirometry testing, 10 A-T adolescents performed spirometry on three separate occasions. Results. Total lung capacity (TLC) was normal or just mildly decreased in 12/15 adolescents tested. TLC correlated positively with functional residual capacity (FRC), a measurement independent of patient effort (R 2 ¼ 0.71). The majority of individuals had residual volumes (RV) greater than 120% predicted (10/15) and slow vital capacities (VC) less than 70% predicted (9/15). By spirometry, force vital capacity (FVC) and forced expiratory volume in 1 sec (FEV 1 ) values were reproducible in the 10 individuals who underwent testing on three separate occasions (R ¼ 0.97 and 0.96 respectively). Seven of the 10 adolescents had FEV 1 /FVC ratios >90%. Conclusion. Lung volume measurements from A-T adolescents revealed near normal TLC values with increased RV and decreased VC values. These findings indicate a decreased ability to expire to residual volume rather then a restrictive defect. Spirometry was also found to be reproducible in A-T adolescents suggesting that spirometry testing may be useful for tracking changes in pulmonary function over time in this population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pulmonary function in adolescents with ataxia telangiectasia

McGrath‐Morrow¹,

Lefton‐Greif²,

Rosquist³

et al. 2007

Pediatric Pulmonology

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“…ILD was present in 25 (25.8%) out of 97 patients with A-T who had either chronic respiratory symptoms or pulmonary disease listed as cause of death [32]. None of these patients had evidence of an infectious process preceding the onset of their lung disease.…”

Section: Interstitial Lung Diseasementioning

confidence: 99%

“…The ILD of A-T is distinctive in its histology, which is uniquely characterised by lung fibrosis and chronic inflammation with lymphocytic or lymphohistiocytic cells, and the presence of atypical epithelial and interstitial cells with large hyperchromatic and pleiomorphic nuclei. Bronchoalveolar lavage fluid contains >70% lymphocytes, 20% macrophages, <5% neutrophils and no eosinophils or neoplastic cells [32]. The response to corticosteroids is discussed later [32].…”

Section: Interstitial Lung Diseasementioning

confidence: 99%

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

et al. 2015

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Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.

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“…It needs to be considered in any patient with A-T who has chronic respiratory symptoms, especially a persistent dry cough, as only treatment with systemic corticosteroids early in the course of the illness is associated with clinical and radiographic improvement [20]. Other non-infective causes of diffuse lung diseases (which may mimic ILD) in A-T include pulmonary parenchymal involvement secondary to lymphoma [21,22] and pulmonary fibrosis secondary to chemotherapy for the treatment of a malignancy [23].…”

Section: Interstitial Lung Disease/pulmonary Fibrosismentioning

confidence: 99%

Ataxia telangiectasia: why should the ERS care?

Bhatt

Bush

Gerven³

et al. 2015

Eur Respir J

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Neurological and immunological contributions to lung disease in A-T require proactive and multidisciplinary management http://ow.ly/TqT44 Why indeed should we care? The answer is that ataxia telangiectasia (A-T) patients will present to respiratory paediatricians for diagnosis, when standard testing, if the diagnosis is not made, may do irreparable harm; and both adult and paediatric respiratory physicians will be involved in managing the respiratory disease, which is a major cause of morbidity and mortality. So there is a real “need to know” which is why the ERS convened a task force on A-T, whose findings are published in the European Respiratory Review [1]. A-T is an autosomal recessive, progressive, multisystem disease caused by mutations in the gene ATM (Ataxia-Telangiectasia Mutated) (11q22.3). This gene is expressed ubiquitously and encodes ATM kinase, a serine/threonine protein kinase, which is involved in signalling following cellular stress. It activates over a hundred proteins involved in the DNA damage response, cell cycle regulation and other pathways. ATM has important roles in neuroprotection, both adaptive and innate immunity, inflammatory responses, metabolism (e.g. insulin signalling), longevity and fertility. It has been estimated that a human cell is confronted with one million DNA lesions every day, placing DNA damage response mechanisms in a position of paramount importance. This has to be a very precise and efficient system to prevent cells with damaged DNA from dividing further or being passed on through germline mutation. The DNA double strand break (DSB) represents one of the most cytotoxic DNA lesions. DSBs can be generated by exposure to ionising radiation or various chemical compounds [2]. The Orphanet registry estimates the average prevalence of A-T to be 1 per 100 000 children [3]. A-T has a large number of other complex and diverse manifestations that vary with age. Neurological symptoms, particularly progressive cerebellar ataxia and abnormalities of the eye movements appear from an early age, and malignant disease is common. Some children first come to medical attention because of recurrent sino-pulmonary infections (which affect ∼50% of children with A-T). Oculocutaneous telangiectasia may not occur until 4 or 5 years of age, so this clue is not available in early life. Laboratory tests may show an elevated alpha-fetoprotein level, immunological deficiencies and chromosomal instability; one lesson is to have a low threshold for the measurement of alpha-fetoprotein as a screening test, especially in young children with infections plus another sign, especially drooling or ataxia. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer, hence the importance of receiving respiratory management right from the start. Also, it is good to consider the diagnosis before rather than after embarking on radiological investigations such as high-resolution computed tomography (HRCT), given the sensitivity of the patients to radiation. There is n...

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Interstitial lung disease in patients with ataxia‐telangiectasia

Cited by 76 publications

References 20 publications

Pulmonary function in adolescents with ataxia telangiectasia

Pulmonary function in adolescents with ataxia telangiectasia

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

Ataxia telangiectasia: why should the ERS care?

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