Predictors of exacerbation in Japanese patients with severe asthma: Analysis of the severe asthma research program (Okayama-SARP) cohort.

BACKGROUND: Because exacerbation of severe asthma decreases patients' quality of life, this study aimed to identify predictive factors for asthma exacerbation. METHODS: Japanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program). RESULTS: A total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51-72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV1 (%FEV1) at enrollment were 204 (IQR, 49-436)/µL, 28 (IQR, 15-43) ppb, 172 (IQR, 56-473) IU/mL, and 80.0 (IQR, 61.1-96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period. CONCLUSIONS: Exacerbation during the previous year, low ACT score, and low %FEV1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor.

An immunocompetent case of chronic pulmonary aspergillosis caused by Aspergillusviridinutans.

We encountered an extremely rare immunocompetent case of chronic pulmonary aspergillosis (CPA) caused by Aspergillus viridinutans. A 74-year-old woman was admitted with fever and hemoptysis. Chest computed tomography revealed a nodule in the left upper lobe. Bronchoscopy was performed, and the transbronchial biopsy specimen revealed Aspergillus fungi. Treatment of the nodule was initially ineffective with voriconazole but effective with liposomal amphotericin B. The causative organism was later identified as A. viridinutans based on the gene sequence of ß-tubulin. This is the first immunocompetent case of CPA caused by A. viridinutans.

Acute Hemorrhagic Rectal Ulcer Complicated by Cytomegalovirus Enteritis following Steroid Pulse Therapy for Acute Exacerbation of Interstitial Pneumonia.

We herein report a rare case of acute hemorrhagic rectal ulcer (AHRU) complicated by cytomegalovirus enteritis following steroid pulse therapy for interstitial pneumonia. An 86-year-old woman underwent steroid pulse therapy for interstitial pneumonia. She was bedridden with dyspnea and suddenly developed melena. Colonoscopy revealed AHRU, which did not improve with conservative treatment, but did improve with ganciclovir administration for cytomegalovirus enteritis. This gastrointestinal complication has not received much attention by pulmonologists who perform steroid pulse therapy for interstitial pneumonia. Delayed treatment of this complications can be fatal. Caution should be taken when administering steroid pulse therapy to bedridden patients with interstitial pneumonia.

Dramatic improvement in innominate artery compression syndrome with only postural changes in a bedridden elderly patient.

We present the case of a bedridden elderly patient who demonstrated dramatic improvement in innominate artery compression syndrome with postural changes alone. A 94-year-old woman presented with dyspnea. Physical findings revealed stridor in the right-sided decubitus position. Her symptoms did not improve with conventional asthma treatment. Plain computed tomography revealed tracheal compression by the bent innominate artery. Contrast-enhanced computed tomography with postural changes altered the compression sites of the organs, resolving the tracheal stenosis. The number of similar bedridden elderly patients will increase in an aging society. We report this case to aid physicians in managing such patients.

A case of nonmucinous pulmonary micropapillary adenocarcinoma mimicking pulmonary tuberculosis.

We report a rare case of nonmucinous pulmonary micropapillary adenocarcinoma mimicking pulmonary tuberculosis. A 68-year-old woman was hospitalized with hemoptysis. Her computed tomography revealed cavities and tree-in-bud appearance similar to the extensive form of pulmonary tuberculosis. However, histopathological findings of transbronchial biopsies of all lesions revealed adenocarcinoma and no pulmonary tuberculosis. Tree-in-bud appearance may relate to the floating micropapillary tufts in alveolar spaces. If pulmonary carcinoma is complicated by pulmonary tuberculosis, patients must be isolated and disadvantaged in cancer treatments. Therefore, recognizing this case may be therapeutically useful for respiratory physicians treating both diseases.

Successful Treatment of Antifungal Combination Therapy with Inhaled Liposomal Amphotericin B and Oral Voriconazole for Intractable Chronic Progressive Pulmonary Aspergillosis.

We experienced a case of the successful treatment of intractable pulmonary aspergillosis with inhaled liposomal amphotericin B (L-AMB) and oral voriconazole (VRCZ). A 52-year-old man was admitted to our hospital with a fever. Chest computed tomography (CT) revealed an infiltrative shadow. Two separate sputum cultures detected Aspergillus niger. Although we treated the patient with single and combined antifungal agents, the infiltrative shadow worsened. After obtaining sufficient informed consent from the patient, we switched him to an inhaled L-AMB. The infiltrative shadow subsequently improved. The patient has remained well for one year without exacerbation. We herein report the usefulness of inhaled L-AMB and oral VRCZ.

Nintedanib can be used safely and effectively for idiopathic pulmonary fibrosis with predicted forced vital capacity ≤ 50%: A multi-center retrospective analysis.

BACKGROUND: Nintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%. METHODS: This was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months. RESULTS: 45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib. CONCLUSIONS: Our data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment.

Usefulness of a selective neutrophil elastase inhibitor, sivelestat, in acute lung injury patients with sepsis.

BACKGROUND: Neutrophil elastase plays a crucial role in the development of acute lung injury (ALI) in patients with systemic inflammatory response syndrome (SIRS). The clinical efficacy of the neutrophil elastase inhibitor, sivelestat, for patients with ALI associated with SIRS has not been convincingly demonstrated. The aim of this study was to determine if there are clinical features of patients with this condition that affect the efficacy of sivelestat. METHODS: This was a retrospective study of 110 ALI patients with SIRS. Clinical information, including the etiology of ALI, the number of organs failing, scoring systems for assessing the severity of illness, and laboratory data, was collected at the time of diagnosis. Information on the number of ventilator-free days (VFDs) and changes in PaO(2)/F(I)O(2) (ΔP/F) before and 7 days after the time of ALI diagnosis was also collected. The effect of sivelestat on ALI patients was also examined based on whether they had sepsis and whether their initial serum procalcitonin level was ≥0.5 ng/mL. RESULTS: There were 70 patients who were treated with sivelestat and 40 control patients. VFDs and ΔP/F were significantly higher in the treated patients than in the control patients. However, there was no significant difference in the patient survival rate between the two groups. Sivelestat was more effective in ALI patients with a PaO(2)/F(I)O(2) ratio ≥ 140 mmHg or sepsis. Sivelestat significantly prolonged survival and led to higher VFDs and increased ΔP/F in septic patients and patients with initial serum procalcitonin levels ≥ 0.5 ng/mL. CONCLUSION: The results may facilitate a future randomized controlled trial to determine whether sivelestat is beneficial for ALI patients with sepsis.

Variant angina pectoris associated with FOLFOX4 therapy.

The patient was a 71-year-old man who underwent a right hemicolectomy for ascending colon cancer (pT3, pN1, pM0) and who opted not to receive adjuvant chemotherapy. Eight months later, multiple liver metastases occurred. He therefore received FOLFOX4 (5-fluorouracil/leucovorin and 85 mg/m(2) oxaliplatin) therapy, up to a total of 5 courses, and showed a partial response. While receiving the sixth course of FOLFOX4, he complained of chest pain and systemic itching approximately 15 min after the start of chemotherapy. An electrocardiogram revealed typical signs of ischemia. Coronary arteriography showed that the coronary arteries were intact. Believing the chest pain to be merely coincidental, we continued with the same therapy. However, he again developed the same chest pain during the seventh cycle of FOLFOX4 and treatment was stopped. We concluded that the patient's symptoms were due to acute coronary syndrome (ACS) associated with the FOLFOX4 regimen. Variant angina as a type of ACS is a rare adverse effect of FOLFOX4. Clinicians should be aware of this potential adverse effect when monitoring patients receiving FOLFOX4.

Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer.

PURPOSE: Although there are several reports concerning gemcitabine-induced interstitial lung disease (ILD), the risk factors for ILD are not well known. In addition, data comparing the incidence and pattern of ILD associated with gemcitabine treatment in patients with non-small-cell lung cancer (NSCLC) versus those with pancreatic cancer are scarce. METHODS: We reviewed clinical records of 118 patients treated with gemcitabine between November 2004 and November 2010. The radiographic findings and other relevant clinical data were reviewed to identify patients who had developed ILD associated with gemcitabine treatment. RESULTS: Out of these 118 patients, we identified 62 patients with NSCLC (group A) and 56 patients with pancreatic cancer (group B), which were then analysed. After gemcitabine administration, ILD was detected in 9 out of the total 118 patients (7.6%). Three patients had grade 2 ILD and 6 patients had grade 3 ILD. Multivariate analysis revealed that prior thoracic radiotherapy (odds ratio: 26.3) and pre-existing pulmonary fibrosis (PF) (odds ratio: 6.5) were correlated with ILD occurrence, but the incidence of ILD was not different between groups A and B. The median dose of gemcitabine administered till the manifestation of ILD tended to be lower in group A than in group B. CONCLUSIONS: Prior thoracic radiotherapy and pre-existing PF were correlated with higher ILD rate in gemcitabine-treated patients. ILD incidence did not differ between NSCLC and pancreatic cancer patients, which may be due to the differences in treatment strategy and tumour properties.

An oral fluoropyrimidine agent S-1 induced interstitial lung disease: A case report.

A 66-year-old Japanese man with pancreatic cancer received eleven courses of gemcitabine monotherapy. The tumor responded to gemcitabine until metastatic liver tumors progressed. Subsequently, he was treated with S-1, an oral fluoropyrimidine anticancer agent, as salvage chemotherapy. Forty-two days after initiating S-1, he presented with dyspnea and fever. Chest computed tomography showed diffuse interstitial lesions with thickening of the alveolar septa and ground glass opacity. Serum KL-6 level was elevated to 1,230 U/mL and he did not use any other drugs except insulin. Thus, the development of interstitial lung disease (ILD) was considered to be due to S-1. Arterial blood oxygen pressure was 49.6 Torr in spite of oxygen administration (5 L/min). Steroid therapy improved his symptoms and the interstitial shadows on chest radiograph. Although S-1-induced ILD has mostly been reported to be mild, clinicians should be aware that S-1 has the potential to cause fatal ILD.

Synchronous double primary lung cancers with different response to pemetrexed.

We describe the case of a 74-year-old male patient with synchronous double primary lung cancers: adenocarcinoma in the right lower lobe and squamous cell carcinoma in the left upper lobe (LUL). These tumors were difficult to differentiate radiographically from a single metastatic primary cancer, but their eventual diagnoses were triggered by their responses to chemotherapy, which included pemetrexed. After two courses of chemotherapy with pemetrexed and carboplatin, the right lower lobe mass had partially resolved; however, the LUL mass had increased. When S-1 was used as fourth-line chemotherapy, the size of the LUL mass decreased. Pemetrexed is a potentially useful drug for treating nonsquamous cell carcinoma, but may not be appropriate in cases with a coexisting squamous cell carcinoma. Our experience with this interesting case leads us to propose that S-1 monotherapy may provide a treatment option in pemetrexed-refractory cases.

A case of pulmonary sclerosing hemangioma surrounded by giant cystic change on high-resolution computed tomography.

Pulmonary sclerosing hemangioma is a rare benign neoplasm, usually presenting as a well-defined round or oval mass. We report a case of pulmonary sclerosing hemangioma surrounded by an unusual giant cystic change on high-resolution computed tomography, which led to the suspicion of this tumor.

Cavitary pulmonary involvement of diffuse large B-cell lymphoma transformed from extra nodal marginal zone B-cell lymphoma MALT type.

We describe a case of pulmonary diffuse large B-cell lymphoma (DLBCL), which was thought to arise from extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 68-year-old woman presented with a 2-month history of cough and bloody sputum. The chest X-ray and computed tomography revealed a mass with cavitation in the right lower lobe. Transbronchial biopsy specimens revealed a granulomatous infiltration without malignant cells. However, diagnosis of MALT lymphoma was established from gastric biopsy specimen. Subsequently, a right lower lobectomy was performed because of hemoptysis. Examination of the resected specimen revealed a diffuse large B-cell lymphoma, which was considered to have transformed from MALT lymphoma, because both lung and stomach lesions had the chromosomal translocation t(11;18)(q21;q21) in common. In addition, there were no nodules, masses, alveolar or interstitial infiltrates in the lung fields, which are usually observed in the case of marginal zone B-cell lymphoma of bronchial mucosa-associated lymphoid tissue. These findings indicate that involvement of DLBCL have to be considered in patients with MALT lymphoma and cavitary lesion of the lung.

Centrally located squamous cell carcinoma of the lung mimicking endobronchial tuberculosis.

Here we report a case of centrally located squamous cell carcinoma of the lung mimicking endobronchial tuberculosis. On the basis of the white light bronchoscopic (WLB) findings, bronchial tuberculosis was initially suspected. But transbronchial biopsy of the lesion revealed squamous cell carcinoma. Autofluorescence imaging bronchovideoscopy (AFI) showed the lesion area as magenta. After four cycles of chemotherapy, the magenta area was markedly shrunk on AFI. Performance of AFI might be useful for differentiating centrally located lung cancer from endobronchial tuberculosis.