Genomic evolutional analysis of surgical resected specimen to assess osimertinib as a first-line therapy in two patients with lung cancer harboring EGFR mutation: Case series.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is crucial for patients with lung cancer harboring EGFR mutations. However, almost all patients experience disease progression, regardless of their response to the targeted therapy, necessitating the development of additional treatment options. Two patients with lung cancer harboring EGFR-L858R mutations in exon 21 were treated by surgical resection during successful osimertinib treatment. Because the pathological diagnosis was suspected to be pleural metastasis, osimertinib treatment was continued until disease progression. We analyzed the evolution of genomic alterations and the levels of AXL using tumor specimens obtained by repeated biopsies during the course of treatment: initial diagnosis, operation, and disease progression. Genetic alterations detected at the three time points were dramatically changed and showed reductions in numbers, while EGFR-L858R mutations were detected in all samples tested in both patients. Immunohistochemical expression of AXL remained positive from the beginning of analysis to disease progression. Clonal evolution under oncogenesis is related to gradual accumulation of genomic alterations during tumor growth. However, our case series revealed that volume reduction procedures may cause this phenomenon. Therefore, identification of intrinsic drug-resistant cells in tumors may be as important as detection of acquired genetic alterations.

Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome with Pembrolizumab for Lung Squamous Cell Carcinoma: A Case Report.

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs). There are a few case reports of remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) as an irAE. We herein report a 49-year-old Japanese man who developed acute-onset polyarthralgia and edema of the back of both hands and bilateral lower legs after pembrolizumab administration for lung cancer. The patient's lung cancer was in complete remission, leading to the diagnosis of RS3PE induced by pembrolizumab rather than malignancy. When patients show RS3PE during ICI treatment, rheumatologists should consider the possibility of an irAE after excluding malignancy and systemic diseases.

A phase 2 trial of durvalumab treatment following radiation monotherapy in patients with non-small cell lung cancer ineligible for stage III chemoradiotherapy: The SPIRAL-RT study.

BACKGROUND: Although concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard treatment for patients with stage III non-small cell lung cancer (NSCLC), only half of the patients are allowed to receive CCRT in real-world settings. We evaluated the efficacy and safety of durvalumab after radiation monotherapy for NSCLC patients who are ineligible for chemoradiotherapy. METHODS: A single-arm, prospective, open-label, multicenter phase II trial was conducted in Japan. The patients received radiation (54-66 Gy) followed by durvalumab (10 mg/kg every 2 weeks for up to 12 months). The primary endpoint was the 1-year progression-free survival (PFS) rate. The secondary endpoints were the objective response rate (ORR), PFS, overall survival (OS), and safety. RESULTS: Between September 2019 and April 2021, 33 patients were enroled from eight institutions. The median patient age was 79 years, and the majority of patients were male (78.8%). The 1-year PFS rate was 39.1% (90% confidence interval [CI]: 24.7-54.6%). Three patients (9.1%) had a performance status of 2. The ORR was 42.4% (95% CI: 27.2-59.2%). The median PFS and OS were 8.9 (95% CI: 7.4-19.4) and 20.8 (95% CI: 15.8-not estimable) months, respectively. The most common adverse event was radiation pneumonitis (51.5%). The median treatment duration was 6.4 (range: 0.50-12.0) months for durvalumab. At the endpoint, 30.3% (10/33) of the patients had completed 1 year of durvalumab therapy. CONCLUSIONS: Durvalumab is an effective treatment with tolerable toxicity following radiation monotherapy in stage III NSCLC patients who are ineligible for chemoradiotherapy. TRIAL REGISTRATION: JMA-IIA00434 (jRCT).

Prophylactic treatment of dacomitinib-induced skin toxicities in epidermal growth factor receptor-mutated non-small-cell lung cancer: A multicenter, Phase II trial.

BACKGROUND: Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. METHODS: We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR-activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. RESULTS: In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32-83 years), 20 were male, and 36 had a performance status of 0-1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%-56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression-free survival was 6.8 months (95% CI, 4.0-8.6 months) and median OS was 21.6 months (95% CI, 17.0 months-not reached). CONCLUSION: Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.

Bronchial Thermoplasty Attenuates Cough Reflex Sensitivity in Severe Asthma : A Single-Center Retrospective Study with 2-year Follow-up.

Despite the relatively short follow-up period in our previous study, we had reported that increased cough reflex sensitivity (CRS) may predict the efficacy of bronchial thermoplasty (BT) for treating asthma. Herein, we examined whether CRS predicts the efficacy of BT 2 years after the final BT treatment. We also investigated the influence of BT on CRS. We reviewed 10 patients 2 years after their final BT treatment. CRS, asthma-related symptoms, asthma exacerbations, and cough-related quality of life were assessed at baseline and 2 years after BT. Five patients responded positively to BT (BT responders) and their asthma control improved. No significant difference in CRS at baseline was detected between the BT responders and nonresponders. In contrast, BT responders exhibited significant improvements in CRS 2 years after BT. CRS at baseline could not predict the BT efficacy after 2 years. This is the first report demonstrating BT desensitized CRS in consecutive case series. J. Med. Invest. 70 : 271-275, February, 2023.

Ramucirumab Plus Docetaxel for Patients with Non-small cell Lung Cancer with Brain Metastases: A Multicenter, Open-Label Single-Arm Phase II Trial.

BACKGROUND: Ramucirumab plus docetaxel combination therapy (DOC/RAM) for advanced non-small cell lung cancer (NSCLC) achieves favorable outcomes; however, efficacy and safety for patients with brain metastases are still unclear. METHODS: Eligible patients included those with advanced NSCLC with measurable asymptomatic brain metastases that progressed after chemotherapy. Patients were intravenously administered ramucirumab (10 mg/kg) and docetaxel (60 mg/m2) every 21-day cycle. RESULTS: Due to difficulties in accumulating the planned 65 participants, enrollment was terminated early when 25 patients were enrolled. Primary endpoint: Median progression-free survival (PFS) was 3.9 months (95% CI, 1.8-5.3). Secondary endpoints: Median intracranial progression-free survival was 4.6 months (95% CI, 2.5-5.9); median overall survival was 20.9 months (95% CI, 6.6-not possible to estimate); objective response rate was 20% (95% CI, 6.8-40.7); disease control rate was 68% (95% CI, 46.5-85.1). The most common grade 3 or higher toxicities were neutropenia in 10 patients (40%). Neither intracranial hemorrhage nor grade 5 adverse events were observed. Patients with higher serum soluble vascular endothelial growth factor receptor 2 concentrations at the start of treatment had slightly longer PFS. CONCLUSION: No clinical concerns were identified with DOC/RAM for NSCLC with brain metastases in this study. Further investigation with a larger sample size is needed to determine the tolerability and safety of these populations (Trial Identifiers: University Hospital Medical Information Network in Japan [UMIN000024551] and Japan Registry of Clinical Trials [jRCTs071180048]).

Utility of beta-human chorionic gonadotropin in pleural effusions: Report of an autopsy case of a male patient with primary pulmonary choriocarcinoma.

A 69-year-old male patient presented with bloody pleural fluid effusion and elevated beta-human chorionic gonadotropin (ß-hCG) levels obtained by thoracentesis. The patient's condition rapidly deteriorated, and he died. The autopsy revealed primary pulmonary choriocarcinoma. Early diagnosis of choriocarcinoma based on ß-hCG levels in the pleural fluid may be possible.

Clinical impact of amrubicin monotherapy in patients with relapsed small cell lung cancer: a multicenter retrospective study.

Background: Topoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear. In the present study, we aimed to evaluate the efficacy of second-line amrubicin in patients with relapsed SCLC who were previously treated with platinum-based chemotherapy, including topoisomerase I and II inhibitors. Methods: This study retrospectively analyzed patients with ES-SCLC who experienced recurrence and were treated with amrubicin at 22 institutions in Japan between April 2015 and November 2020. The progression-free survival of amrubicin monotherapy was investigated using the Kaplan-Meier method. Results: A total of 320 patients were enrolled in this study, with 59 (18%) receiving platinum plus topoisomerase I inhibitor irinotecan and 261 (82%) receiving platinum plus topoisomerase II inhibitor etoposide as first-line treatment. The progression-free survival of amrubicin was significantly longer in the irinotecan group than in the etoposide group (3.2 vs. 2.5 months; P=0.034). Conclusions: These results showed that different types of topoisomerase inhibitors could affect the efficacy of amrubicin monotherapy in the second-line treatment of patients with relapsed ES-SCLC.

A Real-World Analysis of Immune Checkpoint Inhibitor-Based Therapy After Osimertinib Treatment in Patients With EGFR-Mutant NSCLC.

Introduction: The use of immune checkpoint inhibitors (ICIs) with chemotherapy has increased the survival of patients with advanced NSCLC. Nevertheless, the efficacy of ICI treatment for NSCLC with EGFR mutations is limited. Previous studies have not evaluated the efficacy of ICI treatment after osimertinib treatment in real-world settings. Methods: This study performed a retrospective analysis of the association between clinical characteristics and ICI efficacy in patients with EGFR-mutant NSCLC treated with ICIs after osimertinib treatment at 12 institutions in Japan from March 2016 to March 2021. Results: Among 80 patients with EGFR-mutant lung cancer, 42 received ICI monotherapy and 38 received chemoimmunotherapy. In the chemoimmunotherapy group, the progression-free survival (PFS) was significantly longer in the group that exhibited PFS more than 10 months with osimertinib than in the group that exhibited PFS less than or equal to 10 months with osimertinib (8.4 mo versus 3.8 mo, p = 0.026). Nevertheless, there was no significant difference in PFS in the ICI monotherapy group (1.7 mo versus 1.5 mo, p = 0.45). Regardless of the EGFR mutation subtype, PFS of osimertinib treatment was a predictor of the PFS of chemoimmunotherapy (exon 19 deletion mutation: p = 0.03 and exon 21 L858R mutation: p = 0.001). Conclusions: The PFS of osimertinib might be a predictor of PFS of chemoimmunotherapy in patients with EGFR-mutant NSCLC. Further clinical investigations on the predictors of efficacy of administering ICIs after osimertinib treatment are required.

Long-Term Survival of Patients With Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor Monotherapy in Real-World Settings.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is more effective than cytotoxic chemotherapy in improving overall survival (OS) among patients with advanced-stage non-small cell lung cancer (NSCLC). Recently, chemotherapy combined with ICI has been found to yield good outcomes. However, ICI monotherapy is still considered an important treatment option. Data on long-term progression-free survival (PFS) and OS in real-world settings are limited. PATIENTS AND METHODS: This was a multicenter retrospective observational study. A total of 435 consecutive patients histologically diagnosed with advanced, metastatic, or recurrent NSCLC treated with ICI monotherapy were enrolled in this study from December 2015 to December 2018. Clinical data were collected from electronic medical records and pharmacy databases. RESULTS: The PFS and OS of the patients were 3.4 and 13.0 months, respectively. The objective response and disease control rates were 22.8% and 54.9%, respectively, and the 4-year survival rate was 17.9%. Multivariate analyses revealed that elder patients (>70 years), good Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, programmed death-ligand 1 tumor proportion score (PD-L1 TPS) of ≥ 50%, absence of bone metastasis, and presence of immune-related skin toxicity, which is an immune-related adverse event, were correlated with good PFS. Moreover, good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good OS. CONCLUSIONS: The 4-year survival rate was 17.9%. Good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good PFS and OS.

Fractional analysis of bronchoalveolar lavage in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: The utility of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains controversial. Fractional analysis of BAL (FBAL) is a technique that can analyze small airways and alveolar compartments separately and has proven informative in other ILDs. The aim of this study was to explore FBAL characteristics across the spectrum of SSc-ILD severity. METHODS: We retrospectively reviewed patients with SSc-ILD who underwent bronchoscopy with FBAL using three 50 mL aliquots of saline solution. These aliquots were analyzed separately for differential cell composition (FBAL-1, -2, and -3). We compared the FBAL cell composition to the progression of ILD and end-stages of ILD using Cox proportional hazards models. RESULTS: Sixty-eight patients with SSc-ILD were enrolled in this study. The percentage of neutrophils and eosinophils was lower in FBAL-3 compared to FBAL-1. In contrast, the percentage of macrophages and lymphocytes was higher in FBAL-3. Neutrophils in FBAL-2, -3, and the estimated total FBAL cell fraction (FBAL-total) were negatively correlated with the forced vital capacity % predicted (r=-0.420, -0.362, -0.409, respectively). Although FBAL-total was not linked to the progression and end-stage of ILD, a high percentage of neutrophils in FBAL-3 was significantly associated with the development of end-stage ILD (HR 1.093, 95% CI: 1.003-1.190). CONCLUSIONS: A higher percentage of neutrophils in FBAL-3 is correlated with development of end-stage ILD in SSc-ILD as well as mortality.

Two cases of chronic obstructive pulmonary disease evaluated by dynamic-ventilatory digital radiography for pulmonary function and assessment of treatment efficacy.

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.

Suitability of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration versus Paired Transbronchial Biopsy Specimens for Evaluating Programmed Death Ligand-1 Expression in Stage III and IV Lung Cancer: A Comparative Retrospective Study.

Objectives: Cancer cells usually escape tumor-reactive T-cell responses using immune checkpoint proteins, such as programmed death protein-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1). These proteins can be blocked by immune checkpoint inhibitors (ICIs); the decision on ICI-based first-line treatment for advanced lung cancers depends on the PD-L1 levels in tumor specimens. Determining the PD-L1 expression conventionally requires histological specimens from resected tumors and core biopsy specimens. Non-small cell lung cancer (NSCLC) is usually diagnosed at stage III or IV; therefore, only small biopsy specimens, such as those obtained via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are available. However, the suitability of EBUS-TBNA specimens determining the PD-L1 expression levels in advanced lung cancers remains unclear. Materials and Methods: Here, we investigated the concordance rate of PD-L1 expression between EBUS-TBNA and matched transbronchial biopsy (TBB) specimens. Using the 22C3 anti-PD-L1 antibody (immunohistochemistry), we determined the PD-L1 expression levels in paired specimens obtained from 69 patients (50 with advanced NSCLC and 19 with small cell lung cancer [SCLC]), as well as the efficacy of ICIs in these patients. Results: The concordance rate of PD-L1 expression between the EBUS-TBNA and TBB specimens was 78.3%. The κ values referent to the PD-L1-positive expression rate between EBUS-TBNA and TBB specimens were 0.707 and 0.676 at cutoff limits of ≥1% and ≥50%, respectively. Among the 19 SCLC patients, 16 (84.2%) exhibited no PD-L1 expression in both EBUS-TBNA and TBB specimens. Notably, the progression-free survival of patients with ≥50% PD-L1 expression in the paired specimens who received ICI treatment was 8.3 months. Conclusion: Collectively, our results validate the use of EBUS-TBNA specimens for the determination of the PD-L1 expression levels in the context of NSCLC and SCLC.

Late-onset programmed cell death protein-1 inhibitor-induced pneumonitis after cessation of nivolumab or pembrolizumab in patients with advanced non-small cell lung cancer: a case series.

Awareness of the immune-related adverse event of programmed cell death protein-1 (PD-1) inhibitor-induced pneumonitis is important. Herein, we report the clinical course of 3 patients suspected to have PD-1 inhibitor-induced pneumonitis after cessation of PD-1 inhibitor treatment. In case 1, a 62-year-old man was diagnosed with stage IVA adenocarcinoma. Nivolumab monotherapy was prescribed as second-line therapy and later discontinued due to financial reasons. Seven months after the final administration of nivolumab, the patient developed what we diagnosed as nivolumab-induced pneumonitis. The patient was immediately prescribed prednisolone (1 mg/kg p.o. daily), and the pneumonitis resolved after 1.5 months. In case 2, a 68-year-old man was diagnosed with stage IVB squamous cell carcinoma. Nivolumab monotherapy was prescribed as fourth-line therapy. After the second administration of nivolumab, the patient developed what we diagnosed as nivolumab-induced pneumonitis; nivolumab was discontinued, and the patient was immediately prescribed prednisolone (1 mg/kg p.o. daily). Eight months after the final administration of nivolumab, the patient again developed nivolumab-induced pneumonitis. The pneumonitis resolved without additional medication. In case 3, a 69-year-old man was diagnosed with stage IVB adenocarcinoma. Pembrolizumab monotherapy was initiated as sixth-line therapy, and it was discontinued after 4 cycles due to disease progression. Four months after the final dose of pembrolizumab, the patient developed what we diagnosed as pembrolizumab-induced pneumonitis. The patient immediately received a high intravenous dose of methylprednisolone (1,000 mg per day for three days). The pneumonitis and respiratory failure progressed, and he died 8 weeks after the onset of the pneumonitis. We report pneumonitis after discontinuation of ICIs in 3 patients. We confirm that, although uncommon, PD-1 inhibitor-induced irAEs can develop after treatment discontinuation. Further accumulation of cases and clarification of the clinical features of patients with irAEs, such as the time of onset, imaging findings, and treatment outcomes are needed.

Molecular features of tumor-derived genetic alterations in circulating cell-free DNA in virtue of autopsy analysis.

In cancer patients, circulating cell-free DNA (cfDNA) includes tumor-derived DNA (tDNA). cfDNA has been used clinically for non-invasive gene mutation testing. The aim of this study was to characterize the features of the genetic alterations detected in cfDNA. This study included 6 patients with primary lung cancer who died due to cancer progression. Tumors were biopsied at autopsy. Genetic alteration profiles were obtained using next generation sequencing. The features of the tDNA genetic alterations detected in cfDNA included a higher frequency of being present in multiple tumors (67% truncal mutations, 36% shared mutations, and 4% individual mutations) and a higher variant allele frequency (VAF; 47.6% versus 4.1% for tDNA alterations detected in cfDNA versus not detected in cfDNA, respectively). The data revealed that the tumor-derived genetic alterations most easily detected in cfDNA were truncal mutations with a high VAF. These results showed that essential genetic alterations enriched in cfDNA could help to characterize cancer cells and that genetic testing using cfDNA has advantages in the detection of fundamental regulatory aberrations occurring during tumorigenesis.

NOTCH alteration in EGFR-mutated lung adenocarcinoma leads to histological small-cell carcinoma transformation under EGFR-TKI treatment.

BACKGROUND: Molecular targeted therapy has been developed as an innovative treatment for metastatic cancer. Epidermal growth factor receptor (EGFR) mutation is one of the most important and frequent oncogenic drivers in non-small-cell lung cancer, and EGFR-tyrosine kinase inhibitors are indispensable drugs for mutation-positive patients. Currently, the acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a problem, the mechanism of which has not been elucidated. The histological transformation from original adenocarcinoma to small-cell carcinoma is rare; however, it has been detected in many cases after EGFR-TKI treatment. This study aimed to evaluate mutational status in two different histological types and further elucidate the molecular pathogenesis. METHODS: Three patients with EGFR-mutant lung cancer who underwent a histological transformation to small-cell carcinoma after growth factor receptor-TKI treatment were enrolled in this study. Two samples per patient were collected from histologically different lesions, and DNA samples were extracted from formalin-fixed, paraffin-embedded tumor tissues. The paired samples were subjected to next-generation sequencing of 160 cancer-related genes. Based on the sequencing results, the expression levels of related proteins were validated using reverse-transferase polymerase chain reaction and immunohistochemical staining. RESULTS: The following five variants were common among the three cases: MTOR, JAK1, NOTCH2, CSF1R, and MAP2K2. The former four variants were additive to small-cell carcinoma, and the last variant was lost. Both TP53 and Rb1 alterations were detected in adenocarcinoma. Notch2 expression was negative in small-cell carcinoma in both reverse-transcriptase polymerase chain reaction analysis and immunohistochemical staining. ASCL1 expression increased after histological transformation detected using both methods in one case, only these samples were evaluable. CONCLUSIONS: Notch and ASCL1 signaling are the master regulators of neuroendocrine differentiation in small-cell lung carcinoma. Our results suggest that the Notch-ASCL1 axis may also play an essential role in the transformation of small-cell carcinoma under TP53 and RB1 inactivation.

Severe coronavirus disease 2019 (COVID-19) pneumonia patients treated successfully with a combination of lopinavir/ritonavir plus favipiravir: Case series.

The combination therapy of Lopinavir/Ritonavir plus Favipiravir might be a treatment option for patients with COVID-19. Serum ferritin levels and lymphocytopenia are promising markers for disease severity and disease progression that are commonly available in general clinical practice.

Methacholine-induced cough as an indicator of bronchodilator-responsive cough.

BACKGROUND: Cough variant asthma (CVA) is the most common cause of chronic cough and responds well to bronchodilator therapy. Previous studies on methacholine -induced cough have shown that heightened cough response due to bronchoconstriction is a feature of CVA. The aim of this study was to assess Mch-induced cough as an indicator of bronchodilator-responsive cough (BRC). METHODS: This was a single-center retrospective study of prolonged/chronic cough cases who underwent evaluation via spirometry, FeNO and bronchial challenge testing using Mch and capsaicin (C5). Resultant bronchoconstriction after Mch challenge was assessed by flow-volume curves measuring the expiratory flow of the partial flow-volume curve 40% above residual volume (PEF40) and FEV1. BRC was defined as a decrease in cough with bronchodilator therapy by 30% or more on a visual analog scoring scale. RESULTS: Of the 100 patients evaluated, 63 were diagnosed with BRC. Mch-induced cough at a decrease in PEF40 of 35% (PC35-PEF40) was predictive of BRC on AUROC analysis with an AUC of 0.82 (95% CI 0.73-0.90) and cut-off of 24. The AUC for C5, FeNO and PC20-FEV1 were 0.65, 0.47, and 0.58, respectively. CONCLUSION: Compared to C5, FeNO and PC20-FEV1, Mch-induced cough better supports a diagnosis of BRC.