Shared Mechanisms of Lung Injury and Subsequent Fibrosis: Role of Surfactant Proteins in the Pathogenesis of Interstitial Pneumonia in Hermansky-Pudlak Syndrome

Azuma, Arata

doi:10.2169/internalmedicine.44.529

Cited by 5 publications

(4 citation statements)

References 8 publications

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“…Bosentan, an antagonist of endothelin 1 receptors has been tested in a prospective randomised trial (BUILD 2) in SSc-ILD and failed to show beneficial effect. Pirfenidone 76 and N-acetyl cysteine 77 showed beneficial effect in patients with IPF and should be evaluated in SSc-ILD. Finally, imatinib, dazatinib, other tyrosine kinase inhibitors are promising and evaluated in a number of ongoing studies.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Therapeutic options for systemic sclerosis related interstitial lung diseases

Mouthon

Bérezné

Guillevin

et al. 2010

Respiratory Medicine

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Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) mainly encountered in patients with diffuse disease. Unlike idiopathic interstitial pneumonias (IIP), SSc associated ILD corresponds to non-specific interstitial pneumonia (NSIP) in most cases, whereas usual interstitial pneumonia (UIP) is encountered less frequently. This explains the better prognosis of SSc associated ILD compared to IIP. However, severe restrictive lung disease represents one of the two main causes of disease-related death in SSc patients. The treatment of SSc associated ILD is not very well established. Anti-fibrosing treatments have failed to demonstrate any benefit and cyclophosphamide, which has been used in the treatment of this condition for about 15 years, has recently been evaluated in two prospective randomised studies which showed a significant but modest effect on respiratory function. Since none of the patients included in retrospective or prospective studies were selected on the basis of progression of ILD, and since only a minority of SSc patients develop severe ILD, further studies should focus on the subgroup of SSc patients with worsening ILD. A subgroup of patients with rapidly progressive ILD might benefit from pulsed intravenous cyclophosphamide combined with prednisone 15 mg daily but this remains to be confirmed.

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Section: Therapeutic Perspectivesmentioning

confidence: 99%

Therapeutic options for systemic sclerosis related interstitial lung diseases

Mouthon

Bérezné

Guillevin

et al. 2010

Respiratory Medicine

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“…Acute exacerbation of idiopathic pulmonary fibrosis has been shown to portend a poor prognostic sign as these episodes have been shown to be associated with progressive respiratory decompensation and death in this population despite aggressive life support measures [80,81,82]. Given this fact, an independent data and safety monitoring board recommended that the pirfenidone study be aborted earlier than anticipated, as it was unethical to have the compound unavailable to control group participants [83]. Likewise, endpoints of the study could not be assessed adequately and final conclusions could not be drawn reliably.…”

Section: Treatmentmentioning

confidence: 99%

“…Adverse effects such as photosensitivity, vomiting, abnormal hepatic function, and facial paralysis were associated with drug usage, with photosensitivity being the most prevalent. However, those effects ceased or were mitigated by decreasing the dose or temporarily discontinuing the medication [83]. …”

Section: Treatmentmentioning

confidence: 99%

Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

et al. 2006

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Hermansky-Pudlak syndrome (HPS) is a rare heterogeneously inherited autosomal recessive group of disorders presenting with oculocutaneous albinism, bleeding diathesis and pulmonary disease. HPS is thought to occur as a consequence of disturbed formation or trafficking of intracellular vesicles, most importantly, melanosomes, platelet dense granules and lysosomes. The latter finding, in particular, contributes much to the morbidity associated with the disease, as ceroid lipofuscin deposits in lysosomes affect many organ systems. This is especially problematic in the lungs where it is often associated with pulmonary fibrosis and premature death. Currently, there are 7 known HPS genes in humans. In the mouse, at least 16 known HPS genes produce HPS-mutant phenotypes. The HPS gene mutation is considered to be one of the most prevalent single-gene disorders in northwest Puerto Rico, home to the largest cohort of known patients. In HPS, interventions addressing the bleeding diathesis and pulmonary fibrosis are often disappointingly ineffectual. Pirfenidone, a novel compound with documented anti-inflammatory, antioxidant and antifibrotic effects, appears to hold promise in delaying or preventing fibrosis. To date, there has been one successful lung transplant performed on a patient with HPS. We present a patient with HPS and review the current literature on our understanding of this rare disorder.

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“…This hypothesis is also supported by the observation that patients with the Hermansky-Pudlak syndrome (HPS) may develop pulmonary fibrosis. HPS is a genetically heterogeneous disorder caused by abnormal trafficking of proteins to lysosomes that, in the lung, results in abnormal lamellar bodies and impaired surfactant secretion [52][53][54][55][56]. Familial ILD associated with deficient SP-C expression but no identifiable SFTPC mutation [57], and patients with clinical and pathology findings consistent with surfactant dysfunction in whom mutations in either SFTPC or ABCA3 (or SFTPB) were not identified have been reported [48,50 •• ].…”

Section: Adenosine Triphosphate-binding Cassette Protein Member A3mentioning

confidence: 99%

Genetics of pediatric interstitial lung disease

Nogee

2006

Current Opinion in Pediatrics

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Identification of genes responsible for pediatric interstitial lung diseases provides the opportunity for noninvasive testing to establish an etiologic diagnosis, to counsel family members for their recurrence risk, and to classify these rare disorders more accurately. A better understanding of the cause and pathophysiology of these disorders may provide additional insights into the causes of other forms of pediatric interstitial lung diseases, and may suggest novel treatment approaches.

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Shared Mechanisms of Lung Injury and Subsequent Fibrosis: Role of Surfactant Proteins in the Pathogenesis of Interstitial Pneumonia in Hermansky-Pudlak Syndrome

Cited by 5 publications

References 8 publications

Therapeutic options for systemic sclerosis related interstitial lung diseases

Therapeutic options for systemic sclerosis related interstitial lung diseases

Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

Genetics of pediatric interstitial lung disease

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