Two Siblings With Interstitial Lung Disease

Callahan, Sean J.; Pal, Kavita; Gómez, Diana Carolina Salinas; Stoler, Mark H.; Mehrad, Borna

doi:10.1016/j.chest.2017.12.020

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…In some cases, pulmonary disease has been the clinical manifestation that drives diagnosis in adults. Progressive dyspnea (with ILD on imaging) prompted a clinical workup and resulting diagnosis of ASMD in two adult siblings age 52 and 61 years, [ 32 ]. Pulmonary morbidities in chronic ASMD, including respiratory infections and respiratory failure, contribute to early mortality [ 7 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults

Lachmann

Diaz

Wasserstein

et al. 2023

Orphanet J Rare Dis

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Background Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults. An ongoing, open-label, long-term study (NCT02004704) assessed the safety and efficacy of olipudase alfa in 5 adults with ASMD. Results: After 6.5 years of treatment, there were no discontinuations, no olipudase-alfa-related serious adverse events, and no new safety signals compared to earlier assessments. Most treatment-emergent adverse events were mild in intensity (1742/1766, 98.6%). Among treatment-related adverse events (n = 657), more than half were considered infusion-associated reactions (n = 403, 61.3%) such as headache, nausea, abdominal pain, arthralgia, pyrexia, and fatigue. No patient developed neutralizing anti-drug antibodies to cellular uptake, and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Improvements (decreases) in spleen and liver volumes progressed through 6.5 years (mean changes from baseline of -59.5% and -43.7%, respectively). There was a mean increase in diffusing capacity of the lung for carbon monoxide from baseline of 55.3%, accompanied by improvements in interstitial lung disease parameters. Lipid profiles at baseline indicated dyslipidemia. All patients had sustained decreases in pro-atherogenic lipid levels and increases in anti-atherogenic lipid levels following olipudase alfa treatment. Conclusions Olipudase alfa is the first disease-specific treatment for ASMD. This study demonstrates that long-term treatment with olipudase alfa is well-tolerated and is associated with sustained improvements in relevant disease clinical measures. NCT02004704 registered 26 November 2013, https://clinicaltrials.gov/ct2/show/NCT02004704?term=NCT02004704&draw=2&rank=1.

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Section: Discussionmentioning

confidence: 99%

Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults

Lachmann

Diaz

Wasserstein

et al. 2023

Orphanet J Rare Dis

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“…However, careful review of the literature indicated that such lung appearance of chronic visceral ASMD has been noticed previously. Callahan et al described in 2018 two siblings with ILD in the course of chronic visceral ASMD [ 15 ]. One of them experienced recurrent spontaneous pneumothorax and HRCT revealed upper-lobe-predominant paraseptal emphysema in addition to lower-lobe ILD.…”

Section: Discussionmentioning

confidence: 99%

Combined Emphysema and Interstitial Lung Disease as a Rare Presentation of Pulmonary Involvement in a Patient with Chronic Visceral Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

Opoka¹,

Wyrostkiewicz²,

Radwan-Röhrenschef³

et al. 2020

Am J Case Rep

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Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: eleven years of observation

McGovern

Wasserstein

Bembi

et al. 2021

Orphanet J Rare Dis

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Background Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults. Results Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries. Disease characteristics were assessed at baseline, after 1 year, and at the final visit (ranging from 4.5 to 11 years). Thirty patients (51%) were < 18 years at baseline (median age 12 years), and 29 were adults (median age 32 years). Overall, 32/59 patients completed the final visit, 9 died, 9 discontinued, and 9 were lost to follow up. Common clinical characteristics that tended to worsen gradually with time were splenomegaly, hepatomegaly, interstitial lung disease, lung diffusion capacity (DLCO), and dyslipidemia. Spleen volumes ranged from 4 to 29 multiples of normal at baseline, and splenomegaly was moderate or severe in 86%, 83%, and 90% of individuals at baseline, year 1, and final visits, respectively. The proportion of all individuals with interstitial lung disease was 66% (39/59) at baseline and 78% (25/32) at the final visit, while median % predicted DLCO decreased by > 10% from baseline to the final visit. Nine patients died (15%), eight of causes related to ASMD (most commonly pneumonia); of these eight patients, five (63%) had symptom onset at or before age 2. Overall, six of the nine deaths occurred before age 50 with three occurring before age 20. Individuals with either severe splenomegaly or prior splenectomy were ten times more likely to have died during the follow-up period than those with smaller or intact spleens (odds ratio 10.29, 95% CI 1.7, 62.7). Most children had growth deficits that persisted into adulthood. Conclusions This study provides important information about the natural history of chronic ASMD and provides a longitudinal view of the spectrum of disease manifestations and major morbidities in children and adults and supports the selection of clinically meaningful endpoints in therapeutic trials.

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Two Siblings With Interstitial Lung Disease

Abstract: A 52-year-old white woman and her 61-year-old white brother separately presented with gradually worsening dyspnea on exertion and cough, and evidence of interstitial lung disease on chest imaging.

Cited by 3 publications

References 12 publications

Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults

Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults

Combined Emphysema and Interstitial Lung Disease as a Rare Presentation of Pulmonary Involvement in a Patient with Chronic Visceral Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: eleven years of observation

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