Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial

Shulgina, Ludmila; Cahn, Anthony; Chilvers, Edwin R.; Parfrey, Helen; Clark, Allan; Wilson, Emily; Twentyman, Orion P.; Davison, AG; Curtin, John J.; Crawford, Michael; Wilson, Andrew M.

doi:10.1136/thoraxjnl-2012-202403

Cited by 161 publications

(158 citation statements)

References 28 publications

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“…The only observational evidence comes from RICHTER et al [40], who in 2008 demonstrated positive BAL cultures (for known pathogens including Haemophilus, Streptococcus and Pseudomonas) in eight of 22 stable IPF patients. More recently a large multicentre, randomised, placebocontrolled study evaluated the prophylactic use of 12 months of septrin as a treatment for IPF [41]. The authors reported that there was no difference in the primary end-point of change in vital capacity when comparing septrin and placebo.…”

Section: The Role Of Bacteria In the Pathogenesis Of Ipfmentioning

confidence: 99%

The role of infection in the pathogenesis of idiopathic pulmonary fibrosis

2013

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Idiopathic pulmonary fibrosis (IPF) is a progressive, and invariably fatal, condition that is believed to arise in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. The exact triggers, which initiate the fibrotic process, remain unknown. Infectious agents, including both viruses and bacteria, have the capacity to cause alveolarepithelial cell injury and apoptosis. Relatively few studies have examined the role of infection in IPF. Those that have, point to viruses playing a key role as cofactors in the initiation and progression of IPF. There is also some evidence to suggest that viral infection may be responsible for a proportion of acute exacerbations of IPF. The role played by bacteria in the pathogenesis of IPF is less clear cut. Studies from other respiratory diseases suggest that alterations in the lung microbiome are associated with disease and that these changes influence disease behaviour. Emerging molecular microbiological techniques are making the study of microbial communities in the lung easier. It is hoped that by combining such techniques with the careful longitudinal phenotyping of patients with IPF, it will be possible to elucidate the role played by bacteria and viruses in the pathogenesis of the disease. If infection plays a causal role in IPF then it is possible that therapeutic strategies, utilising currently available antiviral or antibiotic drugs, may be effective in modifying the course of this devastating condition.@ERSpublications Understanding viral and bacterial involvement in IPF could help development of novel therapeutic approaches

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Section: The Role Of Bacteria In the Pathogenesis Of Ipfmentioning

confidence: 99%

The role of infection in the pathogenesis of idiopathic pulmonary fibrosis

2013

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“…1 Forty-four percent of all patients with IPF are expected to die within 5 years, compared with 33% of patients with ILDassociated connective tissue disease and 2% of patients with pulmonary sarcoidosis, two other ILDs. 1 Treatments for IPF have been largely unsuccessful, 2,3 mainly because the underlying mechanisms of IPF are unresolved and there is no biomarker available to pinpoint individuals with the risk of accelerated disease progression. Biomarkers in IPF refl ecting states of active fi brogenesis in the lung are needed to indicate those patients who will rapidly decline, so as to prioritize them for intensive management care and lung transplantation.…”

Section: Fibulin-1 Levels In Tissuementioning

confidence: 99%

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

Jaffar

Unger

Corte

et al. 2014

CHEST

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BACKGROUND:The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. Th is progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fi bulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fi brosis in IPF.

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“…67,139,140 FVC or VC decline has been used as a marker of disease progression in many RCTs among IPF populations 62,141,142 and guidelines recommend that an absolute decrease in FVC of ≥ 10% can be used as a surrogate marker for mortality. 140 Recent work has indicated that a relative decline in FVC may be similarly prognostic of mortality.…”

Section: Model Structurementioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: a systematic review and economic evaluation

Loveman

Copley

Colquitt

et al. 2015

Health Technology Assessment

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available.ObjectivesTo conduct a systematic review of clinical effectiveness and an analysis of cost-effectiveness of treatments for IPF based on an economic model informed by systematic reviews of cost-effectiveness and quality of life.Data sourcesEleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, and The Cochrane Library and the Centre for Reviews and Dissemination databases, were searched from database inception to July 2013. Reference lists of relevant publications were also checked and experts consulted.MethodsTwo reviewers independently screened references for the systematic reviews, extracted and checked data from the included studies and appraised their risk of bias. An advisory group was consulted about the choice of interventions until consensus was reached about eligibility. A narrative review with meta-analysis was undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Parameter values were obtained from NMA and systematic reviews. Univariate and probabilistic sensitivity analyses were undertaken. The model perspective is NHS and Personal Social Services, and discount rate is 3.5% for costs and health benefits.ResultsFourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, threeN-acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good, with a low risk of bias. The current evidence suggests that some treatments appear to be clinically effective. The model base-case results show increased survival for five pharmacological treatments, compared with best supportive care, at increased cost. General recommendations cannot be made of their cost-effectiveness owing to limitations in the evidence base.LimitationsFew direct comparisons of treatments were identified. An indirect comparison through a NMA was performed; however, caution is recommended in the interpretation of these results. In relation to the economic model, there is an assumption that pharmacological treatments have a constant effect on the relative rate of per cent predicted forced vital capacity decline.ConclusionsFew interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported.Study registrationThis study is registered as PROSPERO CRD42012002116.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial

Cited by 161 publications

References 28 publications

The role of infection in the pathogenesis of idiopathic pulmonary fibrosis

The role of infection in the pathogenesis of idiopathic pulmonary fibrosis

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

The clinical effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: a systematic review and economic evaluation

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