A critical assessment of treatment options for idiopathic pulmonary fibrosis

Shah, Nirav R.; Noble, Paul W.; Dubois, Robert W.

doi:10.1016/s0012-3692(16)46920-5

Cited by 11 publications

(11 citation statements)

References 8 publications

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“…In the most serious cases, lung transplantation may represent the only viable option for therapy [42]. Conceptually, IPF pathogenesis is now thought to be a primarily fibrotic process rather than an inflammatory one [43], although it is well-recognized that subsets of macrophages play a significant role in either limiting or enhancing lung fibrosis [44]–[46].…”

Section: Discussionmentioning

confidence: 99%

Chlamydia pneumoniae Infection in Mice Induces Chronic Lung Inflammation, iBALT Formation, and Fibrosis

et al. 2013

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Chlamydia pneumoniae (CP) lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5×105 CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs). Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis.

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Section: Discussionmentioning

confidence: 99%

Chlamydia pneumoniae Infection in Mice Induces Chronic Lung Inflammation, iBALT Formation, and Fibrosis

et al. 2013

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“…Interstitial lung diseases were diagnosed by investigators based on the criteria for fibrosing interstitial pneumonia according to 2 factors: (i) HRCT findings showed UIP or “possible” UIP (“inconsistent” UIP without peribronchovascular predominance were excluded from this study) according to an official American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association statement: idiopathic pulmonary fibrosis (2011) ; and (ii) other than other known cause of ILD (eg, infection, drug toxicity, occupational environmental exposures, and connective tissue disease) were excluded . Patients with “mild” or “moderate” ILD were included in this study (severe ILD was excluded) based on 3 factors: (i) forced vital capacity less than 65%; (ii) desaturation with exertion (PaO 2 less than 88% at room air); and (iii) diffusing capacity of the lung for CO 50% or less . Mild ILD was defined as having none of these 3 factors, and moderate ILD was as having any 1 of these factors (severe ILD had 2 or 3 of these factors).…”

Section: Methodsmentioning

confidence: 99%

Phase II study of nab‐paclitaxel + carboplatin for patients with non‐small‐cell lung cancer and interstitial lung disease

et al. 2019

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The prognosis of non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is poor, and 5%-20% of those receiving chemotherapy experience ILD exacerbation. To evaluate the safety and efficacy of nab-paclitaxel plus carboplatin for NSCLC patients with ILD, we undertook a multicenter phase II study. Chemotherapynaïve patients with advanced NSCLC and mild or moderate ILD received nab-paclitaxel (100 mg/m 2 , days 1, 8, and 15) plus carboplatin (area under the curve = 6, day 1) every 3 weeks for 4 cycles (maximum, 6 cycles). Interstitial lung diseases were diagnosed based on criteria for fibrosing interstitial pneumonia. The primary endpoint was the prevalence of exacerbation-free ILD 28 days after completion of protocol treatment.Secondary endpoints were response rate, progression-free survival, overall survival, prevalence of exacerbation-free ILD, and toxicity. Ninety-four patients were enrolled, and 92 patients received any protocol treatment. Median age was 70 years, and 58% had nonsquamous histology. In the primary analysis, the prevalence of exacerbationfree ILD 28 days after protocol treatment was 95.7% (88/92; 90% confidence interval, 90.3-98.5), which met the primary endpoint. Response rate was 51% (95% confidence interval, 40%-62%). At the time of data cut-off, median progression-free survival was 6.2 months, and median overall survival was 15.4 months. The most common grade 3/4 adverse events were neutropenia (75%), leukopenia (53%), anemia (48%), and thrombocytopenia (20%). Two treatment-related deaths (1 each of pulmonary infection and ILD exacerbation) were observed. This study showed that a combination of nab-paclitaxel with carboplatin was tolerable in NSCLC patients with mild or moderate ILD in terms of safety. This study is registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN 000012989). K E Y W O R D Scarboplatin, exacerbation, interstitial lung disease, nab-paclitaxel, non-small-cell lung cancer | 3739 KENMOTSU ET al

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“…However, anti-inflammatory compounds have produced poor therapeutic results in the treatment of PF. Similarly, corticosteroids combined with immunosuppressants such as cyclophosphamide or azathioprine, colchicine, and other agents have provided no more than 30% improvement in objective indices (Morawiec et al, 2011;Shah et al, 2005). Therefore, new therapeutic agents based on novel mechanisms with improved efficacy are needed to ameliorate or slow the progression of fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Suppression of nuclear factor erythroid 2-related factor 2 via extracellular signal-regulated kinase contributes to bleomycin-induced oxidative stress and fibrogenesis

Li¹,

Chen²,

Bai³

et al. 2013

Toxicology Letters

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A critical assessment of treatment options for idiopathic pulmonary fibrosis

Cited by 11 publications

References 8 publications

Chlamydia pneumoniae Infection in Mice Induces Chronic Lung Inflammation, iBALT Formation, and Fibrosis

Chlamydia pneumoniae Infection in Mice Induces Chronic Lung Inflammation, iBALT Formation, and Fibrosis

Phase II study of nab‐paclitaxel + carboplatin for patients with non‐small‐cell lung cancer and interstitial lung disease

Suppression of nuclear factor erythroid 2-related factor 2 via extracellular signal-regulated kinase contributes to bleomycin-induced oxidative stress and fibrogenesis

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