Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.

Lynch, Joseph P.; McCune, W. Joseph

doi:10.1164/ajrccm.155.2.9032171

Cited by 150 publications

(184 citation statements)

References 248 publications

(770 reference statements)

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“…18 Symptoms of IP responding to immunosuppression have been described in chronic GVHD. [19][20][21][22][23][24] Both patients had repeated airway infections, which are common in patients with chronic GVHD and which may have caused damage to the airways, increasing the obstruc-tive lung disease in patient 1 in combination with nicotine abuse. 13 An additional crucial factor in patient 2 may have been insufficient immunosuppression in the face of active chronic GVHD and progressive pulmonary fibrosis (lost to follow-up).…”

Section: Discussionmentioning

confidence: 99%

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease

Wolff

Reichenberger

Steiner

et al. 2002

Bone Marrow Transplant

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Summary:Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis. Bone Marrow Transplantation (2002) 29, 357-360. DOI: 10.1038/sj/bmt/1703386 Keywords: bone marrow transplantation; lung fibrosis; graft-versus-host disease; progressive systemic sclerosis; bronchiolitis obliterans; total nodal irradiation Sclerodermoid chronic GVHD (sGVHD) is a well-known late complication in patients with chronic GVHD. 1 It resembles progressive systemic sclerosis and involves the skin, fasciae, as well as the gastrointestinal tract. Furthermore data on cutaneous microchimerism in females with progressive systemic sclerosis may indicate a related pathophysiology. Progressive systemic sclerosis typically affects the kidneys and the lungs with development of alveolitis and pulmonary fibrosis. 5 However, pulmonary or renal involvement have not been reported in sGVHD. In chronic GVHD pulmonary changes are well known. Bronchiolitis obliterans (BO) is the typical and threatening pulmonary manifestation of chronic GVHD with progressive obstruction of the small bronchioles due to proliferation of the peribronchiolar tissue. [6][7][8][9][10][11] The occurrence of pulmonary fibrosis is mainly considered a manifestation of late toxicity of total body irradiation or chemotherapy during conditioning for allogeneic stem cell transplantation or the result of interstitial pneumonitis (IP) mainly due to viral infections or acute GVHD. 12-13 Here, we report two patients with sGVHD and late onset progressive pulmonary fibrosis. Patients Patient 1A 32-year-old male with a 15 pack-year smoking history received a peripheral stem cell graft from his HLA-identical sister for T-ALL in 2nd CR, after conditioning with TBI (12 Gy in six fractions with shielding of the lung, total pulmonary dose 10 Gy) and cyclophosphamide 60 mg/kg once daily i.v. on days 1 and 2. Patient and donor were CMVnegative by serology. GVHD prophylaxis consisted of cyclosporine A (CsA), MTX and prednisone. On day 90, the patient developed primary extensive chronic GVHD of the skin, oral mucosa, salivary glands an...

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Section: Discussionmentioning

confidence: 99%

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease

Wolff

Reichenberger

Steiner

et al. 2002

Bone Marrow Transplant

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“…Initially considered a measure of last resort, corticosteroid use evolved into wide acceptance, notwithstanding their substantial toxicity [Lynch and McCune, 1997]. However, no prospective placebo controlled randomized trial has been performed [Walter et al 2006], their efficacy is unproven [Lynch and McCune, 1997]. With these caveats, the 1999 ATS consensus, recommended treatment daily with 40 to 100 mg of prednisone or prednisolone for 2 to 4 months, with a subsequent gradual taper over the highdose intravenous "pulse" methylprednisolone (1 to 2 g once weekly or biweekly), which has no proven advantage over oral corticosteroids [Gulsvik et al 1986].…”

Section: Treatment "Classics" Treatment Of Pulmonary Fibrosismentioning

confidence: 99%

“…The sporadic use, or small studies with the other cytotoxic chemotherapeutic agents methotrexate [Lynch and McCune, 1997;Douglas et al 2000], chlorambucil [Brown and Turner-Warwick, 1971] and vincristine [Meuret et al 1978] have been reported with no evidence to support the use of any of these agents [Davies et al 2003]. …”

Section: Treatment "Classics" Treatment Of Pulmonary Fibrosismentioning

confidence: 99%

Review: New perspectives in the treatment of idiopathic pulmonary fibrosis

Rogliani

Mura

Porretta

et al. 2008

Ther Adv Respir Dis

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Idiopathic pulmonary fibrosis (IPF) is the most frequent idiopathic interstitial pneumonia with a prevalence ranging from 5 to 15 per 100,000 persons, and above 175 per 100,000 in the older population. IPF is a relentlessly progressive fibrotic lung disorder leading to death within a median duration of 3 years. It was hypothesized in the 1970s that pulmonary fibrosis initiates as an "alveolitis" progressing to interstitial fibrosis with connective tissue deposition, derangement of the lung architecture and functional impairment. However, in vitro studies indicated that alveolar/bronchiolar injured epithelial cells can drive the fibrotic process in the absence of macrophages and with minimal inflammation. This, together with the inability of classic immunosuppressive therapy to cure IPF, generated new pathogenesis paradigms and intense research into the role of the lack or the excessive production of anti-fibrotic or profibrotic mediators, oxidant injury, exaggerated coagulation, thus leading to investigate new treatment strategies. Preliminary results of some of such trials have shown significant reductions in lung function decline, disease exacerbation and mortality.

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“…To date, these drugs have mainly been used as an alternative in refractory cases. On the basis of the available data on safety and efficacy, methotrexate, hydroxychloroquine and azathioprine are currently regarded as the preferred agents in pulmonary sarcoidosis [1,70]. However, most of the published data is anecdotal, with observations made on small numbers of patients.…”

Section: Nonsteroidal Treatmentmentioning

confidence: 99%

Corticosteroid treatment in sarcoidosis

Grutters

Bosch²

2006

European Respiratory Journal

164

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At present there is no curative treatment for sarcoidosis. Immunosuppressive and/or immunomodulatory drugs can, however, be used for controlling the disease.Corticosteroids remain the mainstay of therapy. They function by suppressing the proinflammatory cytokines and chemokines that are involved in cell-mediated immune responses and granuloma formation. Only in a select group of patients is it justifiable to use these drugs, after careful evaluation of the pros and cons. Importantly, disease severity, e.g. threatened organ functions, and not disease activity itself should be the deciding factor in this process.In the case of parenchymal involvement, there is substantial evidence that corticosteroids can improve respiratory symptoms and chest radiography and lung function parameters over 6-24 months. Other generally acknowledged (empirical) criteria for systemic treatment include neurological, cardiac and sight-threatening ocular involvement and hypercalcaemia. Remarkably, despite .50 yrs of use, there is no proof of long-term (survival) benefit from corticosteroid treatment. In addition, there are still no data regarding the optimal dose and duration of corticosteroid or other immunosuppressive therapy.One of the weightiest questions remaining is whether or not these drugs can prevent scarring in patients with a fibrogenic phenotype. As new agents, including infliximab and thalidomide, enter the stage and new diagnostic tools are now available, there is clearly a momentum to design multicentric randomised controlled trials with long enough follow-up (.5 yrs) to answer this pivotal question.

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Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.

Cited by 150 publications

References 248 publications

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease

Review: New perspectives in the treatment of idiopathic pulmonary fibrosis

Corticosteroid treatment in sarcoidosis

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