Efficacy of early antifibrotic treatment for idiopathic pulmonary fibrosis.

BACKGROUND: Although antifibrotic drugs, including nintedanib and pirfenidone, slow the progression of idiopathic pulmonary fibrosis (IPF), there is little data about the timing of start of antifibrotic treatment in real-world clinical practice. The present study aimed to clarify the efficacy of nintedanib and pirfenidone in patients with early-stage IPF. METHODS: We compared survival and disease progression between patients with IPF with Japanese Respiratory Society (JRS) disease severity system stage I with and without oxygen desaturation on the 6-min walk test (6MWT) and increased the gender-age-physiology (GAP) staging. We examined the efficacy of antifibrotic drugs in patients with early-stage IPF. RESULTS: The severity of stage I IPF (n = 179) according to the JRS criteria consisted of the following GAP staging criteria: stage I, 111 cases; stage II, 58 cases; stage III, 10 cases. The duration from the initial visit to disease progression and survival time was significantly shorter in JRS stage I patients with oxygen desaturation on the 6MWT or with increased GAP staging (unfavorable group) compared with patients without those factors. In the unfavorable group, the relative decline in percentage predicted forced vital capacity (%FVC) over 6 months was significantly lower in patients undergoing antifibrotic treatment compared with non-treated patients. CONCLUSION: Antifibrotic drugs have a beneficial effect on the decline in %FVC in Japanese patients with early-stage IPF who have oxygen desaturation on the 6MWT or increased GAP staging.

Tolerability and efficacy of switching anti-fibrotic treatment from nintedanib to pirfenidone for idiopathic pulmonary fibrosis.

BACKGROUND: In real-world studies, the rate of discontinuation of nintedanib (NT) varies from 4% to 53%. Switching anti-fibrotic treatment in patients with idiopathic pulmonary fibrosis (IPF) has not been adequately investigated, and data on the tolerability and efficacy of changes in anti-fibrotic treatment is limited in clinical practice. OBJECTIVE: To identify factors associated with poor continuation of NT, efficacy and predictors of deterioration after switching from NT to pirfenidone (PFD) in patients with IPF. SUBJECTS AND METHODS: One hundred and seventy patients with IPF in whom NT was introduced between April 2017 and March 2022 were included to investigate NT continuation status and the effect of switching to PFD. RESULTS: A total of 123 patients (72.4%) continued NT for 1 year and had a significantly higher %forced vital capacity (FVC) at NT introduction than those who discontinued within 1 year (80.9% ± 16.3% vs. 71.9% ± 22.1%, P = 0.004). The determinant of poor NT continuation was the high GAP stage. On the other hand, 28 of 36 patients who discontinued NT because of disease progression switched to PFD. Consequently, FVC decline was suppressed before and after the change. The predictor of deterioration after the switch was a lower body mass index. CONCLUSIONS: In patients with IPF, early NT introduction increased continuation rates, and switching to PFD was effective when patients deteriorated despite initial NT treatment.

Pleuroparenchymal fibroelastosis in mycobacterium avium complex lung disease.

We report a rare case of pleuroparenchymal fibroelastosis (PPFE) with interstitial lung disease progressed after an onset of mycobacterium avium complex (MAC) lung disease. Clinicians should pay attention to the management for patients with PPFE in MAC lung disease.

Successful baricitinib treatment of refractory anti-synthetase syndrome associated with interstitial lung disease.

A 47-year-old Japanese man was admitted with dyspnoea on exertion (DOE), skin rash and myalgia. Clinical findings of Gottron's sign and mechanic's hands were observed, with increased serum levels of Krebs von den Lungen-6, surfactant protein-D, creatine kinase, and anti-EJ on laboratory tests. In both lungs, chest computed tomography revealed diffuse reticular opacities and lower lobe predominance. The patient was diagnosed with anti-synthetase syndrome (ASS) and associated interstitial lung disease. Despite repeated administration of high-dose intravenous corticosteroids, cyclophosphamide and immunoglobulin, his skin rash, myalgia, and DOE followed a relapsing and remitting course. He was then given rituximab therapy. This was initially successful, but disease activity increased approximately 12 months after starting rituximab therapy. Finally, in addition to prednisolone and cyclosporine A, we administered baricitinib. There has been no relapse of the disease in the 12 months since he began baricitinib treatment.

Coronavirus disease 2019 vaccination-induced acute exacerbation in idiopathic pulmonary fibrosis.

We report a rare case of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) after coronavirus disease 2019 (COVID-19) vaccination. Clinicians should be aware of this COVID-19 vaccination-induced AE in IPF.

Immunoglobulin G4-positive interstitial pneumonia associated with pleuroparenchymal fibroelastosis.

A 79-year-old former smoking Japanese man was admitted to our hospital with a 2-year history of dry cough and dyspnoea on exertion. High-resolution computed tomography of the chest revealed reticulation and perilobular opacity with bronchial wall thickening and ground-glass opacities (GGOs) in both lungs, in addition to subpleural dense consolidation (pleuroparenchymal fibroelastosis-like lesion; PPFE-like lesion) predominantly in the bilateral upper lobes. Serum immunoglobulin G4 (IgG4) was elevated (348 mg/dl). Lung biopsy specimens obtained by video-assisted surgery revealed a mixture of usual interstitial pneumonia (IP) and non-specific IP pattern admixed with PPFE. In addition, immunohistochemical staining of IgG4 showed numerous IgG4-positive plasma cells. Consequently, he was diagnosed with IgG4-positive IP associated with PPFE. We initiated a combination therapy with prednisolone and cyclosporine as a calcineurin inhibitor. During prednisolone tapering, his clinical conditions and GGOs improved gradually over 12 months. However, reticular opacities and PPFE-like lesions remained unchanged, and pulmonary function test findings slightly deteriorated.

Multiple endotracheal metastases of combined small cell lung carcinoma.

We report a very rare case of combined small cell lung carcinoma (C-SCLC) which presented as persistent cough and was due to endotracheal metastases. Clinicians should be aware of this unusual site of metastases from a C-SCLC.

Eosinophilic bronchiolitis successfully treated with benralizumab.

A 53-year-old non-smoking Japanese woman was admitted to our hospital with a 20-year history of wet cough and dyspnoea on exertion. Bronchial asthma (BA) had been diagnosed 20 years earlier. Although she has been treated with high-dose inhaled corticosteroid, she had experienced frequent exacerbation of BA, and short-term oral corticosteroid bursts were occasionally administered. High-resolution CT of the chest revealed diffuse centrilobular nodules with bronchial wall thickening and patchy ground-glass opacities in both lungs. Lung biopsy specimens showed widespread cellular bronchiolitis with follicle formations in the membranous and respiratory bronchioles, accompanied by marked infiltration of plasma cells and eosinophils. In addition, immunohistochemical immunoglobulin G4 (IgG4) staining revealed many IgG4-positive plasma cells, and the ratio of IgG4-positive cells to IgG-positive cells exceeded 40%. The final diagnosis was eosinophilic bronchiolitis with marked IgG4-positive plasma cell infiltration in association with BA. With benralizumab therapy, her clinical condition dramatically improved.

Post-coronavirus disease 2019 organizing pneumonia confirmed pathologically by video-assisted thoracoscopic surgery.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has become a global pandemic. Many survivors of serious COVID-19 pneumonia have long-term residual pulmonary disease. However, there is little documentation of the histopathological characteristics of lung sequelae post-COVID-19 and effective treatments. We present two Japanese cases of lung sequelae post-COVID-19. The patients were histopathologically diagnosed with organizing pneumonia (OP) or OP with fibrosis and no diffuse alveolar damage on video-assisted thoracoscopic surgery. Case 1, who had been diagnosed with OP, was successfully treated with corticosteroid and other immunosuppressive agents over a 6-month period. Although case 2, who had been diagnosed with OP with fibrosis, had a partial and unsatisfactory response to immunosuppressive agents, the patient responded to antifibrotic treatment including nintedanib.

Acute exacerbation in chronic bird fancier's lung with pleuroparenchymal fibroelastosis.

A 71-year-old non-smoker woman was admitted to our hospital complaining of a six-month history of dry cough. She had kept java sparrow for nine years and has been raising budgerigars for the previous eight months. High-resolution computed tomography (HRCT) images of the chest revealed reticulonodular lesions predominantly in the bilateral upper lobes. Surgical lung biopsy specimens showed non-caseous epithelioid cell granulomas in the alveolar spaces, including irregular and centrilobular fibrosis with pleuroparenchymal fibroelastosis. When she started using a duck feather duvet at home, she developed dyspnoea and chest HRCT abnormalities progressively deteriorated. The results of precipitation of antibodies against duck feather, java sparrow, and budgerigars dropping extracts were positive in sera. Consequently, the patient was diagnosed as having chronic bird fancier's lung with acute exacerbation caused by the use of a feather duvet. After combination treatments with corticosteroid and cyclosporine, her respiratory symptoms and reticulonodular shadow immediately improved.

Treatment with antifibrotic agents in idiopathic pleuroparenchymal fibroelastosis with usual interstitial pneumonia.

BACKGROUND: There are no established therapeutic options available for idiopathic pleuroparenchymal fibroelastosis (IPPFE) apart from supportive care and lung transplantation. Furthermore, it is known that IPPFE with a usual interstitial pneumonia (UIP) pattern and lower lobe predominance is a disease entity distinct from idiopathic pulmonary fibrosis (IPF). To our knowledge, few studies are available that report on the efficacy of antifibrotic agents for IPPFE with UIP. AIM: The aim of this study was to compare the efficacy of antifibrotic agents between IPPFE with UIP and typical IPF in real-world clinical practice. PATIENTS AND METHODS: A retrospective analysis was performed on the medical records of all patients at two interstitial lung disease centres. Sixty-four patients were diagnosed as having IPPFE with UIP and 195 patients were diagnosed with typical IPF. We compared the efficacy of antifibrotic agents between these two groups. RESULTS: Survival time was significantly shorter in the patients with IPPFE with UIP. Some 125 patients were administered antifibrotic agents for over 6 months (34 with IPPFE with UIP and 91 with typical IPF). Reduced forced vital capacity (FVC) 6 months after treatment with antifibrotic agents was significantly greater in the IPPFE with UIP group than in those in the typical IPF group. Moreover, the change in % predicted FVC was significantly greater during the follow-up in patients with IPPFE with UIP compared with those with typical IPF. CONCLUSIONS: The efficacy of antifibrotic agents was limited in patients with IPPFE with UIP. Thus, IPPFE with UIP remains a fatal and progressive disease.

Miliary opacities in pulmonary sarcoidosis.

Pulmonary sarcoidosis should be considered in the differential diagnosis of miliary opacities in bilateral upper lobes predominance.

Autoimmune pulmonary alveolar proteinosis presenting peripheral ground-glass opacities.

Autoimmune pulmonary alveolar proteinosis should be considered in the differential diagnosis of peripheral ground-glass opacities.

[Efficacy of domiciliary noninvasive positive pressure ventilation in chronic obstructive pulmonary disease patients].

OBJECTIVE: The aim of this study was to assess the clinical features and efficacy of domiciliary noninvasive positive pressure ventilation (NPPV) in patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We conducted a retrospective study of 16 patients with COPD who received NPPV between March 1996 and April 2005. The patient characteristics, clinical features, a change in arterial PaCO2 and prognoses were evaluated. RESULTS: The study population consisted of 15 males and 1 female, mean age 68.4 +/- 9.9 yrs. The mean values of pulmonary function tests were as follows; FEV1 = 0.73L, FEV1% = 29.8%, VC = 2.49L, %VC = 77.5%, RV/ TLC 55.4%, PaO2 59.8 Torr, PaCO2 71.4 Torr (on admission). Fourteen of 16 patients presented desaturation in the night and 6 patients had sleep apnea syndrome. Eight of the 16 patients received NPPV during acute exacerbation. NPPV yielded dramatic improvement in daytime hypercapnia and clinical symptoms. However, arterial PaCO2 gradually elevated during the long-term clinical course. The duration of treatment was from 2 months to 9 years, with a mean value of 2.3 years. The cause of death of 7 patients was respiratory failure in 5 cases and lung cancer in 2, respectively, and the mortality was significantly higher in patients who received NPPV during acute exacerbation than stable COPD patients receiving NPPV. CONCLUSIONS: Long-term improvement in daytime clinical symptoms and arterial blood gas tensions can be achieved by NPPV in patients with COPD.

[Large cell neuroendocrine carcinoma of the lung incidentally found at surgery for pulmonary aspergillosis].

We report a 56-year-old man with pulmonary large cell neuroendocrine carcinoma (LCNEC) incidentally found at the surgery for pulmonary aspergillosis. In 1991, an abnormal chest radiographic shadow was found on a mass screening. A diagnosis of pulmonary aspergillosis was made by bronchoscopic examination. The patient was then followed up without treatment. He had hemoptysis in 2005, and was referred to our hospital. Chest CT scan revealed a cavitary lesion with an air crescent sign and an irregularly shaped nodule in the right apex. Wedge resection of these lesions was performed under video-assisted thoracoscopic surgery. Pathological examination revealed not only aspergilloma, but also an LCNEC 11 x 7 mm in size, which was located close to the aspergilloma. Microscopically, nests of tumor cells were distributed peribronchially. Right upper lobectomy and mediastinal lymph node dissection was performed, and the pathological stage was IIIA (T1N2M0). The patient received four cycles of adjuvant chemotherapy with carboplatin and paclitaxel. No recurrence has been observed since surgery. This is the first report describing co-existence of pulmonary aspergilloma and LCNEC.

Multiple bronchioloalveolar carcinomas in acromegaly: a potential role of insulin-like growth factor I in carcinogenesis.

The molecular pathogenesis of lung cancer, especially multiple and synchronous bronchioloalveolar carcinomas (BACs), is still unknown. Here, we report two cases of multiple BACs associated with acromegaly, and discuss about the possible relationship between these two pathological condition. The first patient was a 52-year-old female with a history of Hardy's surgery for pituitary growth hormone cell adenoma 2 years earlier. The second patient was a 57-year-old female with acromegaly and obstructive sleep apnea syndrome. Both patients were non-smokers and showed a high serum level of insulin-like growth factor I (IGF-I) at the time of admission, even though the level of growth hormone had decreased. High-resolution computed tomography (HRCT) revealed multiple small nodules with pure ground-glass opacity (GGO) in both lungs of the first patient and a small nodule with pure GGO in the right lung of the second one. Partial resection for these tumors were performed under video-assisted thoracoscopic surgery. Resected lung specimens of the first case revealed one papillary adenocarcinoma, seven BACs, and 11 atypical adenomatous hyperplasias (AAHs). The second case showed two foci of BACs. Immunohistochemically, all BACs were strongly positive for IGF-IR which is a specific receptor for IGF-I, and all AAHs were also weakly positive for IGF-IR. Since IGF-I is known as a potent growth factor for normal as well as cancerous cells, it might play an important role for tumorigenesis and/or tumor progression of BACs through its interaction with and/or upregulation of IGF-IR. In addition, much attention should be paid to detect lung lesions in acromegaly with high serum level of IGF-I.

[Fatal invasive pulmonary aspergillosis triggered by influenza B virus infection in an individual with idiopathic pulmonary fibrosis].

A 56-year-old man with idiopathic pulmonary fibrosis developed acute symptoms, including fever and cough. Chest X-ray and CT scan films revealed consolidations and ground glass opacities in the bilateral lungs suggestive of massive pneumonia and acute respiratory distress syndrome (ARDS). Microscopic examination by a transbronchial lung biopsy from the right middle lobe demonstrated numerous hyphae of aspergillus. Despite treatment with anti-fungal agents, respiratory failure rapidly progressed, and the patient died on the 21st hospital day. Postmortem examination of the lung showed multiple abscesses with hyphae of aspergillus invading into small pulmonary artery and alveoli, which were the characteristic findings of invasive pulmonary aspergillosis (IPA). In addition, diffuse alveolar damage was also present, associated with the typical features of UIP such as honeycombing in the bilateral lungs. The serum anti-influenza B virus antibody was high at 512-fold. Therefore, it was speculated that influenza B virus infection triggered superimposed aspergillus infection leading to fatal IPA associated with ARDS.

[A case of pulmonary abscess in which Haemophilus parainfluenzae and Streptococcus intermedius were isolated by percutaneous needle aspiration].

Some microbes, including the Bacteroides species, Staphylococcus aureus and Streptococcus milleri groups, can cause pulmonary abscess. Haemophilus parainfluenzae is usually categorized as one of the normal flora which colonizes in the ears and the nasopharynx, and it has been long considered that H. parainfluenzae has little pathogenicity in the lower respiratory tract and lung parenchymal. In this report, we present a case of pulmonary abscess caused by both H. parainfluenzae and Streptococcus intermedius. The patient was a 75-year-old man who had had total esophageo-gastrectomy because of esophageal cancer. He presented with purulent sputum, and chest X-ray film showed a dense consolidation in the right upper lung field. CT-guided transcutaneous fine needle aspiration was performed as a diagnostic procedure. Since both H. parainfluenzae and S. intermedius had been isolated from the lesion, pulmonary abscess caused by these two pathogens was diagnosed. The patient was treated with panipenem/betamipron, and his symptoms and pulmonary infiltrates on the chest X-ray film improved thereafter. So far, very few cases have been reported in which H. parainfluenzae caused lower respiratory tract infection. Although S. intermedius is known as one of the pathogens of pulmonary abscess, it is possible that H. parainfluenzae could also be pathogenic in infectious diseases of the lung.

Cyclosporin treatment in steroid-resistant and acutely exacerbated interstitial pneumonia.

OBJECTIVE: The aim of this study was to evaluate the efficacy of cyclosporin A (CsA) in patients with interstitial pneumonia (IP). DESIGN: Retrospective comparative study. PATIENTS: We reviewed 33 patients (23 males and 10 females with a mean age of 62.5 years) with histologically-proven progressive IP who were treated with CsA. All patients had corticosteroid-resistant IP or developed acute exacerbation of IP in their courses. RESULTS: The underlying systemic diseases were: idiopathic interstitial pneumonias (IIPs) in 19 patients, and collagen vascular diseases (CVDs) in 14. The histopathological patterns and underlying diseases of IP were classified as usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) in 10 patients, cellular-nonspecific interstitial pneumonia (NSIP)/IIPs in 3, fibrotic-NSIP/IIPs in 5, organizing pneumonia (OP)/IIP in 1, UIP/CVDs in 4, cellular-NSIP/CVDs in 7, fibrotic-NSIP/CVDs in 2, and diffuse alveolar damage (DAD)/CVD in 1, respectively. They received a low dosage of CsA combined with corticosteroids. The prognoses after treatment with CsA were well correlated with histopathological patterns. Cellular-NSIP and OP showed better prognoses than fibrotic-NSIP, UIP or DAD. In addition, CVDs had better prognoses than IIPs, when compared on the basis of the same histopathological patterns. Furthermore, the prognoses in the CsA-treated group were significantly better than in those without CsA treatment in regard to acute exacerbation of UIP/IPF. CONCLUSIONS: CsA combined with corticosteroids may be an efficacious treatment for corticosteroid-resistant IP and for acute exacerbation of IPF.