Predictors of survival in coexistent hypersensitivity pneumonitis with autoimmune features

Adegunsoye, Ayodeji; Oldham, Justin M.; Demchuk, Carley; Montner, Steven M.; Vij, Rekha; Strek, Mary E.

doi:10.1016/j.rmed.2016.03.012

Cited by 47 publications

(53 citation statements)

References 33 publications

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“…That threshold was selected because of its increased specificity and easy applicability in routine practice. Although germinal centers may be observed in IPF, CTD-ILD, and hypersensitivity pneumonitis, 19,24–26 patients with CTD-ILD are described as having higher germinal center scores than do patients with IPF. 24 Furthermore, patients with hypersensitivity pneumonitis may have up to 2 germinal centers in one high-power field.…”

Section: Discussionmentioning

confidence: 99%

Interstitial Pneumonia With Autoimmune Features: Value of Histopathology

Adegunsoye¹,

Oldham²,

Valenzi³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context Patients with idiopathic interstitial pneumonia may display evidence of autoimmunity, without meeting criteria for a defined connective tissue disease. A recent European Respiratory Society/American Thoracic Society statement proposed research criteria for interstitial pneumonia with autoimmune features (IPAF), which includes findings from the clinical, serologic, and morphologic domains. Objectives To investigate the importance of histopathologic criteria within the morphologic domain and to report our methodology for identifying these features. Design Patients with idiopathic interstitial pneumonia at the University of Chicago, who underwent surgical lung biopsy or lung transplantation were assessed for IPAF histopathologic features, using the initial pathology interpretation in the electronic records. A focused rereview of available slides by a pulmonary pathologist was then performed for patients who failed to meet IPAF criteria on initial pathology assessment. Results Of 422 patients with idiopathic interstitial pneumonia, 176 (41.7%) underwent surgical lung biopsy or lung transplant. Forty-six of those 176 patients (26.1%) met IPAF criteria by initial pathology interpretation and a positive clinical or serologic feature. Of the remaining 130 patients, 73 (56.2%) met either the clinical or serologic domains without meeting the morphologic domain, whereas 36 (27.7%) had slides available for pathology rereview. This rereview demonstrated nonspecific interstitial pneumonia in 8 of 36 patients (22.2%) and lymphoplasmacytic infiltrates in 6 of 36 patients (16.7%), resulting in an additional 7 of 36 patients (19.4%) with idiopathic interstitial pneumonia that met the IPAF criteria. In IPAF, pulmonary vasculopathy was the most prevalent finding (45 of 84; 53.6%) and predicted increased mortality (hazard ratio, 2.5; P = .04). Conclusions Using a methodological approach to identifying IPAF pathology, we demonstrate a significant increase in the number of patients meeting IPAF criteria because of focused pathologic review and highlight the prognostic value of the IPAF pathologic findings.

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Section: Discussionmentioning

confidence: 99%

Interstitial Pneumonia With Autoimmune Features: Value of Histopathology

Adegunsoye¹,

Oldham²,

Valenzi³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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“…Some single-nucleotide polymorphisms (SNP) such as PD-1.1 G/A and PD-1.3 GA were found to be involved in the RA susceptibility4546. Moreover, previous studies also indicated that immune-mediated pneumonitis may be associated with autoimmune process4748. Animal experimental results demonstrated that pneumonitis was concomitant with RA and even shared the same immunity mechanism with RA4950.…”

Section: Discussionmentioning

confidence: 99%

PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis

Hong

Zhang

et al. 2017

Sci Rep

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Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92% (95%CI: 2.18–3.90%) for all-grade and 1.53% (95%CI: 1.15–2.04%) for high-grade pneumonitis. Compared with routine chemotherapy, PD-1 inhibitors were associated with a significant increased risk of pneumonitis. Moreover, among the types of tumor treated with PD-1 inhibitors, the melanoma patients have the lowest incidence of pneumonitis, while the non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) patients have the highest. Furthermore, no significant differences were detected in the incidences of all- and high-grade pneumonitis between high-dose and low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors were probably associated with an increased risk of pneumonitis in a dose-independent manner, compared with routine chemotherapeutic agents. The frequency and severity of treatment-mediated pneumonitis was quite different in patients with various tumor types.

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“…Two chest radiologists (J.H. Chung and S. Montner) reviewed high-resolution computed tomography (HRCT) of patients with CHP, and characterised and scored them for features of fibrosis [ 11 ] (defined as the presence of reticulation, traction bronchiectasis and honeycombing). A systematic, detailed historical assessment of environmental antigen exposures (avian, mould, hot tub and unknown) is performed for all patients in the University of Chicago ILD registry, regardless of referring diagnosis.…”

Section: Methodsmentioning

confidence: 99%

Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

et al. 2017

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In chronic hypersensitivity pneumonitis (CHP), lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival.Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs) and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres.Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA), 93 (71%) received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC) and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04) and 66% less frequent with mycophenolate mofetil (p=0.002). FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings.CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

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Predictors of survival in coexistent hypersensitivity pneumonitis with autoimmune features

Cited by 47 publications

References 33 publications

Interstitial Pneumonia With Autoimmune Features: Value of Histopathology

Interstitial Pneumonia With Autoimmune Features: Value of Histopathology

PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis

Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

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