Acute inflammatory and immunologic responses against antigen in chronic bird-related hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease induced by the inhalation of a wide variety of antigens and a persistent antigen exposure induces inevitably pulmonary fibrosis in chronic HP. Although neutrophils, Th1 and Th17 cells contribute to lung inflammation in acute phase of HP, there is no clear explanation as to how the immunological reaction occurs just after the inhalation of causative antigens in the chronic phase of HP. METHODS: We examined the inflammatory and immunologic profiles before and after the inhalation provocation test (IPT) in serum and bronchoalveolar lavage fluid (BALF) from patients with chronic bird-related HP (BRHP) and other interstitial lung diseases (ILDs). We analyzed BALF samples from 39 patients (19 BRHP and 20 other ILDs) and serum samples from 25 consecutive patients (20 BRHP and 5 other ILDs) who underwent the IPT. RESULTS: A significant increase of neutrophils was observed in the BALF from the BRHP patients following the IPT. Neutrophil chemoattractants, namely, granulocyte colony-stimulating factor, IL-6, IL-8, IL-17, and CXCL2 significantly increased in both the serum and BALF of the BRHP patients after the IPT. Serum IFN-γ and CXCL10, cytokines/chemokines that contributed to Th1 inflammation, were also significantly increased in BRHP following the IPT. CONCLUSIONS: This study demonstrated the exposure to the causative antigen provoked acute neutrophilic and Th1 immunologic responses similar to acute HP even in the chronic phase of HP.

[A case of melioidosis occurring after a long-term stay in Vietnam that developed pulmonary cavitation and relapsed with multiple pulmonary nodules].

A 69-year-old man complained of fever in September 2009, after returning from Vietnam where he has been working for 20 years. He had diabetes mellitus and was on diabetic oral medication. He was examined at a nearby hospital, and found out to have pneumonia with cavity formation in the right upper lobe which was found out to be not due to tuberculosis. Although the patient once recovered with antibacterial medicine, after a few months, in January 2010, he was admitted to our hospital because of recurrent fever. Computed tomography revealed multiple pulmonary nodules which were thought to be pulmonary emboli, as well as subcutaneous abscess, spleen abscess, and kidney abscess. Blood test showed that he also had DIC. As Burkholderia pseudomallei was cultured from the subcutaneous abscess and blood, was diagnosed as melioidosis. The patient was treated with meropenem for 8 weeks, and then a maintenance oral antibacterial medicine was continued for the next 6 months. The patient fully recovered after those treatments and has not relapsed since then. This is the ninth case report of melioidosis in Japan which is an imported infectious disease.

[A case of Churg-Strauss syndrome with subarachnoid hemorrhage and left phrenic nerve paralysis].

A 60-year-old woman was given a diagnosis of Churg-Strauss syndrome (CSS) in 2000 because of peripheral blood eosinophilia, eosinophilic pneumonia, asthma, polyarticular pain, and limb numbness. She was treated with prednisolone (PSL), and the above symptoms improved but then relapsed on tapering of PSL. In September 2009, after 7 days of tapering of PSL to 5mg/day, the patient developed a subarachnoid hemorrhage and was admitted. MRA and cerebral angiography revealed no aneurysm; the source of bleeding could not be determined, but her symptoms indicated a benign course. A chest X-ray 27 days after admission showed left diaphragmatic elevation, and left phrenic nerve paralysis was diagnosed by a phrenic nerve stimulation test. Peripheral blood eosinophilia had progressed gradually during the admission period, and although it is rare for subarachnoid hemorrhage and phrenic nerve paralysis to be associated with CSS, we regarded these as vasculitis symptoms related to CSS.

[Clinical features of reversed halo sign in cryptogenic organizing pneumonia].

Reversed halo sign (RHS) is often seen in computed tomography (CT) scans of cryptogenic organizing pneumonia (COP). To investigate its clinical features, we retrospectively reviewed 30 cases of COP in 13 men and 17 women, whose age range 28 to 73, with a mean of 58.4 years. All diagnoses were made with transbronchial lung biopsy (TBLB), but it took an average of 24.8 days from the first visit until the diagnosis of COP. RHS was seen in 7 cases (23%) and multiple RHSs were seen in 3 cases. We treated 5 cases (71%) with steroids. Their CT images showed parenchymal abnormalities which started as nodular lesions, then enlarged, and then the central lesion changed into ground-glass opacities, until finally, RHS was formed. The presence of RHS does not necessarily indicate a marked difference in the clinical course of COP. In conclusion, in the present series RHS was a phase of the clinical course of COP, and was useful to diagnose COP.

A case of synchronous multiple primary lung adenocarcinomas harboring epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement successfully treated with combination of osimertinib and alectinib.

Synchronous multiple primary lung cancers (SMPLC) should be distinguished from intrapulmonary metastasis to define the optimal treatment approach. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are typically mutually exclusive and the co-existence of both mutations is relatively rare. Herein, we report a case of SMPLC harboring each EGFR mutation and ALK rearrangement successfully treated with combination of osimertinib and alectinib. A combination of EGFR- and ALK-tyrosine kinase inhibitors could be an effective and tolerable therapeutic option for SMPLC with EGFR mutations and ALK rearrangement.

A case of diffuse large B-cell lymphoma originating from chest wall complicated by benign asbestos pleural effusion.

A 78-year-old man with exposure to asbestos was admitted to our hospital for back pain. A chest computed tomography showed right pleural effusion and a significant increase in the size of masses in the right chest wall over an interval of six months. He did not undergo further examinations and expired one month later. Autopsy revealed the presence of diffuse large B-cell lymphoma (DLBCL) and complicated by benign asbestos pleural effusion. We considered that this tumour had originated from the soft tissue in the chest wall based on the radiological and autopsy findings. The present report highlights that primary DLBCL of chest wall might be associated with chronic inflammation due to asbestos-related pleural diseases.

[Clinical features of secondary spontaneous pneumothorax in interstitial pneumonia].

Secondary spontaneous pneumothorax is a critical event in the clinical course of interstitial pneumonia. To investigate its clinical features, we retrospectively reviewed 21 cases (13 men and 8 women, age range 43 to 75, mean age 64.5) of interstitial pneumonia accompanied with pneumothorax, including 14 cases with chronic hypersensitivity pneumonitis, 4 cases of idiopathic interstitial pneumonia, and 3 cases of other etiology of interstitial pneumonia. The mean vital capacity percentage (VC) was 56%, and percentage of diffusing capacity of lung for carbon monoxide (DLco) was 46%. Fourteen cases (67%) were treated with steroids and eight cases (38%) were complicated by Aspergillus infection. The median survival time (MST) from the onset of pneumothorax was 214 days. The dosage of steroids and the frequency of Aspergillus infection were significantly higher in patients whose pneumothorax did not improve than in those whose pneumothorax improved. In conclusion, steroids and Aspergillus infection seem to be associated with the development of pneumothorax and poor outcome in interstitial pneumonia.

Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis.

BACKGROUND: Apolipoprotein A-I (apoA-I) has an antifibrotic effect in idiopathic pulmonary fibrosis. Although pulmonary fibrosis is associated with poor prognosis of patients with hypersensitivity pneumonitis (HP), little is known regarding the role of apoA-I in the pathogenesis of HP. METHODS: Two-dimensional electrophoresis, immunoblotting, and enzyme-linked immunosorbent assays were performed for the identification and quantification of apoA-I in bronchoalveolar lavage fluid (BALF) from patients with acute and chronic HP. To investigate the degradation of apoA-I, apoA-I was incubated with BALF. Moreover, the role of apoA-I in TGF-ß1-induced epithelial-mesenchymal transition of A549 cells was examined. RESULTS: The concentration of apoA-I in the BALF was significantly lower in chronic HP (n = 56) compared with acute HP (n = 31). The expression level of apoA-I was also low in the lung tissues of chronic HP. ApoA-I was degraded by BALF from HP patients. The number of chymase-positive mast cells in the alveolar parenchyma was inversely correlated with apoA-I levels in the BALF of chronic HP patients. In vitro experiment using A549 cells, untreated apoA-I inhibited TGF-ß1-induced epithelial-mesenchymal transition, although this trend was not observed in the chymase-treated apoA-I. CONCLUSIONS: A decrease of apoA-I was associated with the pathogenesis of chronic HP in terms of pulmonary fibrosis and mast cell chymase attenuated the protective effect of apoA-I against pulmonary fibrosis. Furthermore, apoA-I could be a crucial molecule associated with lung fibrogenesis of HP.

Changes in serum KL-6 levels during short-term strict antigen avoidance are associated with the prognosis of patients with fibrotic hypersensitivity pneumonitis caused by avian antigens.

BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is the most common type of fibrotic hypersensitivity pneumonitis (HP). Antigen avoidance (AA) is a key step in the diagnosis and management of HP, but not all fibrotic HP patients improve through AA. Because of the poor prognosis of fibrotic HP, predictive biomarkers to identify patients showing rapid progression during AA are urgently needed. METHODS: From a retrospective review of the medical records of 1941 patients with interstitial lung disease, 75 cases of fibrotic BRHP confirmed by a provocation test or surgical lung biopsy were identified. To identify potential prognostic markers obtained at or around diagnosis, physiological and serological variables at diagnosis and the relative changes in those variables during strict AA were evaluated. Cox proportional hazards models with log-rank testing were used to compare the associations between these variables and survival. RESULTS: Univariate analyses showed that gender, smoking status, and the relative change in the serum levels of Krebs von den Lungen-6 (KL-6) were associated with prognosis (P = 0.02, 0.04, and 0.02, respectively), but the presence of honeycombing and the forced vital capacity were not associated with survival. The relative change in KL-6 levels (greater than vs. less than a 10% decrease) was significantly associated with survival in a stratified analysis (73.9 vs. 34.9 months; P = 0.04). CONCLUSIONS: The relative change in KL-6 levels is associated with the prognosis of patients with fibrotic BRHP independent of previously identified prognostic biomarkers. This finding could help pulmonologists identify fibrotic BRHP patients that are likely to show rapid progression.