Primary Cytomegalovirus Pneumonia Successfully Treated with Corticosteroid Therapy and Valganciclovir.

Cytomegalovirus infection is typically asymptomatic in immunocompetent individuals. A 26-year-old woman was admitted to our hospital with a fever and breathlessness. Chest computed tomography (CT) revealed bilateral diffuse reticulation and nodules. Laboratory investigations showed atypical lymphocytosis and increased transaminases. She was treated with corticosteroid pulse therapy because of acute lung injury, and her clinical condition improved. Based on the presence of cytomegalovirus antibodies, antigen, and polymerase chain reaction findings, she was diagnosed with primary cytomegalovirus pneumonia and treated with valganciclovir. Primary cytomegalovirus pneumonia is very rare in immunocompetent individuals. The efficacy of corticosteroid and valganciclovir against cytomegalovirus pneumonia in this patient is noteworthy.

Two cases of trastuzumab deruxtecan-induced interstitial lung disease in advanced breast cancer.

Trastuzumab deruxtecan (T-DXd) frequently induces interstitial lung disease (ILD) more than other anti-human epidermal growth factor receptor 2 therapies. We diagnosed two cases of ILD induced by T-DXd in patients with advanced breast cancer. The first case is that of a 57-year-old Japanese woman who complained of dyspnoea and fever after 4 cycles of T-DXd. Chest computed tomography (CT) showed diffuse consolidation and a reticular shadow. The second case was that of a 72-year-old Japanese woman who complained of dyspnoea after 3 cycles of T-DXd. Chest CT showed a reticular shadow predominantly in the left lung. Both patients were treated with corticosteroids, including pulse methylprednisolone; however, their general condition weakened due to ILD, long-term corticosteroid therapy and breast cancer progression. Subsequently, the patients were unable to continue chemotherapy for breast cancer. To the best of our knowledge, this is the first report in a real-world clinical setting.

Low-dose oestrogen-progestin associated pulmonary infarction mimicking pneumonia and pleurisy.

A 28-year-old woman with a history of treatment with a low-dose oestrogen-progestin (LEP) formulation presented to our hospital due to right chest pain. She had just been discharged from another hospital for pneumonia and pleurisy which had improved with antibiotics. Contrast-enhanced computed tomography (CT) revealed bilateral pulmonary emboli corresponding to the peripheral consolidations. The pulmonary emboli indicated that the peripheral consolidation was due to pulmonary infarction (PI). No aetiological factors were identified except for the history of LEP therapy. Although the typical CT images of PI are consolidations in the peripheral area, these finding are non-specific for PI. This case of PI was misdiagnosed as infection because of response to antibiotics and similar CT findings. Therefore, careful evaluation of the patient history and clinical findings are imperative for accurate diagnosis. Venous thromboembolism can occur frequently around 3 months after the start of LEP treatment.

Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: a multicenter, retrospective, propensity score-matched study.

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Granulomatous-lymphocytic Interstitial Lung Disease Associated with Good's Syndrome That Responded to Immunoglobulin Therapy.

Good's syndrome is associated with thymoma and acquired immunodeficiency. A 54-year-old man visited our hospital with a complaint of cough. Chest imaging revealed diffuse nodular shadows and anterior mediastinal mass. Hypogammaglobulinemia and a decreased B lymphocyte count were found by a laboratory evaluation. The lung nodules markedly regressed after immunoglobulin therapy. The mediastinal mass and remaining nodule were surgically resected and diagnosed as a type AB thymoma and a necrotizing epithelioid granuloma with T lymphocyte-dominant alveolitis, respectively. The overall appearances of these lesions were mostly in line with the spectrum of granulomatous-lymphocytic interstitial lung disease associated with Good's syndrome.

Idiopathic Pulmonary Hemosiderosis Associated with Emphysematous Change in an Adult Who Underwent Lung Transplantation.

Idiopathic pulmonary hemosiderosis is characterized by repeated alveolar hemorrhaging. We herein report a 52-year-old Japanese woman who had shortness of breath, diffuse small nodules, thin-walled cysts, and bronchiolectasis. A surgical lung biopsy revealed peribronchial hemosiderosis, centrilobular emphysema, and fragile elastic fibers of the alveolar septa and small vessels. She ultimately underwent living-donor lung transplantation five years after the first visit.

Airway-centered Interstitial Fibrosis Involving Smooth Muscle Hyperplasia with Severe Pulmonary Hypertension.

In the 2013 updated classification of the American Thoracic Society/European Respiratory Society, airway-centered interstitial fibrosis (ACIF) is included as a bronchiolocentric pattern of interstitial pneumonia (IP) among idiopathic IPs. We encountered a case of severe pulmonary hypertension (PH) with chronic IP. The patient initially presented with shortness of breath and often lost consciousness due to PH, and seven years after his first visit, he ultimately died. An autopsy revealed ACIF and usual IP. In particular, the ACIF comprised non-atypical smooth muscle hyperplasia, and pulmonary hypertensive vascular degeneration was detected. This case may represent a new pathological feature of ACIF.

Using 6-Min Walk Distance Expressed as a Percentage of Reference to Evaluate the Effect of Pulmonary Rehabilitation in Elderly Patients With Interstitial Lung Disease.

PURPOSE: The aim of this study was to investigate the effect of outpatient pulmonary rehabilitation (PR) program and the use of 6-min walk distance (6MWD), expressed as a percentage of the predicted value (%6MWD), to quantify response to PR in elderly patients with interstitial lung disease (ILD). METHODS: This was a prospective, nonrandomized controlled study. Forty eligible patients with stable ILD (≥65 y old) were advised to attend an outpatient PR program for 3 mo. Thirteen patients completed the PR program and formed the PR group. Ten patients who did not attend the PR program were evaluated after 3 mo and formed the control group. Patients in the PR group underwent a comprehensive 3-mo hospital-based outpatient PR program, consisting of educational support and supervised exercise training, and attended the rehabilitation unit weekly. RESULTS: Change in the absolute 6MWD (Δ6MWD) in the PR group was not significantly different compared with the control group (P = .062). Change in %6MWD (Δ%6MWD) was greater in the PR group than in the control group. Baseline 6MWD was not correlated with Δ6MWD, but baseline %6MWD was significantly correlated with Δ6MWD and Δ%6MWD. CONCLUSION: PR had a beneficial effect on elderly patients with ILD in terms of exercise endurance. %6MWD might be more useful than the absolute 6MWD as an outcome measure of PR and as a predictor of response to PR in elderly patients with ILD.

Xenon-Enhanced Dual-Energy CT Imaging in Combined Pulmonary Fibrosis and Emphysema.

BACKGROUND: Little has been reported on the feasibility of xenon-enhanced dual-energy computed tomography (Xe-DECT) in the visual and quantitative analysis of combined pulmonary fibrosis and emphysema (CPFE). OBJECTIVES: We compared CPFE with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), as well as correlation with parameters of pulmonary function tests (PFTs). METHODS: Studied in 3 groups were 25 patients with CPFE, 25 with IPF without emphysema (IPF alone), 30 with COPD. Xe-DECT of the patients' entire thorax was taken from apex to base after a patient's single deep inspiration of 35% stable nonradioactive xenon. The differences in several parameters of PFTs and percentage of areas enhanced by xenon between 3 groups were compared and analyzed retrospectively. RESULTS: The percentage of areas enhanced by xenon in both lungs were calculated as CPFE/IPF alone/COPD = 72.2 ± 15.1% / 82.2 ± 14.7% /45.2 ± 23.2%, respectively. In the entire patients, the percentage of areas enhanced by xenon showed significantly a positive correlation with FEV1/FVC (R = 0.558, P < 0.0001) and %FEV1, (R = 0.528, P < 0.0001) and a negative correlation with %RV (R = -0.594, P < 0.0001) and RV/TLC (R = -0.579, P < 0.0001). The percentage of areas enhanced by xenon in patients with CPFE showed significantly a negative correlation with RV/TLC (R = -0.529, P = 0.007). Xenon enhancement of CPFE indicated 3 different patterns such as upper predominant, diffuse, and multifocal defect. The percentage of areas enhanced by xenon in upper predominant defect pattern was significantly higher than that in diffuse defect and multifocal defect pattern among these 3 different patterns in CPFE. CONCLUSION: The percentage of areas enhanced by xenon demonstrated strong correlations with obstructive ventilation impairment. Therefore, we conclude that Xe-DECT may be useful for distinguishing emphysema lesion from fibrotic lesion in CPFE.

Acute exacerbation of combined pulmonary fibrosis and emphysema associated with Hermansky-Pudlak syndrome.

A 30-year-old male smoker with congenital amblyopia and oculocutaneous albinism was admitted to our hospital complaining of progressive dyspnea on exertion. Chest computed tomography images revealed diffuse reticular opacities and honeycombing in the bilateral lower lobes with sparing of the subpleural region along with emphysema predominantly in the upper lobes. Lung biopsy specimens showed a mixture of usual interstitial pneumonia and a non-specific interstitial pneumonia pattern with emphysema. Of note, cuboidal epithelial cells with foamy cytoplasm on the alveolar walls and phagocytic macrophages with ceroid pigments in the fibrotic lesions were observed. The patient was diagnosed with Hermansky-Pudlak syndrome (HPS) associated with combined pulmonary fibrosis and emphysema (CPFE). Six years following the patient's initial admission to our hospital, he died from acute exacerbation (AE) of CPFE associated with HPS. This is one of only few reports available on the clinicopathological characteristics of AE in CPFE associated with HPS.

Pathophysiological Implication of Computed Tomography Images of Chronic Pulmonary Aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a refractory disorder that needs long-term antifungal treatment and occasionally results in fatal respiratory failure and hemoptysis. However, the pathological features of the disorder have not been thoroughly delineated. Thirty cases were therefore analyzed clinically and histologically to elucidate the pathophysiology of CPA. The subjects comprised 14 individuals who underwent surgical removal and 16 patients who died. No subject exhibited a severely immunocompromised state. The main symptoms included cough, hemosputum, and dyspnea. Chest computed tomography (CT) findings revealed a cavity, fungus ball, and consolidation and/or ground glass opacity (GGO); 27 serial CT scans showed enlarged consolidation and/or GGO (70%), dilatation of the cavity (26%), and extension to the opposite lung (22%). Histopathological findings revealed a cavity with ulceration, bronchitis, and various degrees of organizing pneumonia (OP) that were correlated with the area of consolidation and GGO on the CT scan. The essential pathophysiology of CPA can be understood as an active state of ulceration of the cavity and/or erosive bronchitis caused by contact with the fungus ball, which may play a significant role in the development of OP. Consequently, OP is thought to reflect respiratory failure that relates to the prognosis of CPA.

Thymoma exhibiting spontaneous regression in size, pleural effusion and serum cytokeratin fragment level: A case report.

A 30-year-old man was admitted to Toho University Omori Medical Center for assessment of right chest pain and fever. Chest computed tomography (CT) revealed an anterior mediastinal tumor sized 11.0×6.0×5.0 cm, with right pleural effusion. The laboratory analysis revealed elevated white blood cell count (11,000/µl), C-reactive protein (4.1 mg/dl) and cytokeratin fragment (CYFRA; 12.7 ng/ml; normal, <2 ng/ml). The level of CYFRA in the pleural effusion was also markedly elevated (143 ng/ml). On the first day after admission (6 days after the initial CT), there was a mild regression on CT (10.0×5.5×4.4 cm; reduction rate, 26.7%), with decrease of the pleural effusion volume. A CT-guided needle biopsy was performed, but the findings were not conclusive, as most of the tissue was necrotic. Seven days later (13 days after the initial CT), a CT revealed further regression (9.5×5.4×4.2 cm; reduction rate, 34.7%) with disappearance of the pleural effusion. The patient was followed up on an outpatient basis. At 35 days after the initial CT, the tumor continued to shrink without treatment (8.0×3.6×3.0 cm; reduction rate, 73.8%) and the serum CYFRA level had decreased to 0.8 ng/ml, although it had not returned to normal levels. At 62 days after the initial CT, the patient underwent surgical resection. The resected specimen was diagnosed as thymoma (World Health Organization type B2; Masaoka classification, stage II), with prominent degeneration and necrosis. One possible cause of the spontaneous regression may be increased internal pressure, probably associated with rapid tumor growth, leading to massive necrosis with resulting chest pain, inflammatory reaction with pleural effusion and subsequent tumor regression. The serum CYFRA level may be a useful marker for the evaluation of the clinical course of thymoma with extensive necrosis.

Histological study of chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) has been accepted the criteria for the diagnosis of pulmonary Aspergillus infection. Whereas, either pathophysiology or signs of CPA remains still controversial. METHODS: In this study, we histopathologically investigated 25 specimens of CPA, surgically resected. RESULTS: 21 (84 %) of that comprised male. There were 21 cases with mild impairment of the immune system and/or a scar mostly due to old tuberculosis. There is a tendency for a negative correlation between peripheral blood white cell numbers and value level of beta-(1,3)-D-glucan. Four cases showed a granular fluorescent signal in granulation tissue surrounding the cavity without the fungal aspects itself. CONCLUSIONS: In conclusion, acute inflammatory exudate along the terminal respiratory tract is most significant pathophysiolocial complication of the CPA, caused to organizing pneumonia, which derives fatal respiratory failure. In addition, the viability of fungus does not concern extension of exudative inflammation at the site of erosion along terminal airway.

Microscopic polyangiitis preceded by combined pulmonary fibrosis and emphysema.

A 73-year-old male metalworker was admitted to our hospital with a 3-year history of progressive dry cough. Chest high-resolution computed tomography revealed emphysematous changes and reticular lesions, which is referred to as combined pulmonary fibrosis and emphysema (CPFE). Surgical lung biopsy specimens revealed unclassified interstitial pneumonia, including a nonspecific interstitial pneumonia pattern and usual interstitial pneumonia pattern. Two years after his first admission he developed rapid progressive renal dysfunction with an elevated level of myeloperoxidase-antineutrophil cytoplasmic antibody (428 EU). A renal biopsy specimen revealed interstitial nephritis and glomerulonephritis. Consequently, microscopic polyangiitis preceded by CPFE was diagnosed. Despite transient exacerbation of renal involvement, his general condition remained mostly stable during a 2-year period of corticosteroid treatment. He ultimately died from severe pneumococcal pneumonia associated with acute lung injury.

Primary Antiphospholipid Syndrome Associated with Diffuse Alveolar Hemorrhage and Pulmonary Thromboembolism.

Antiphospholipid syndrome (APS) is clinically characterized by arterial or venous thrombosis; however, non-thromboembolic lung manifestations, such as diffuse alveolar hemorrhage (DAH), have also been previously reported. DAH is relatively common in APS patients with systemic lupus erythematosus, although it is rare in primary APS. We encountered a 78-year-old man who presented with hemoptysis and dyspnea. Chest CT showed diffuse ground-glass opacity with pulmonary thromboembolism. He was successfully treated with corticosteroids and heparin; however, DAH recurred after the corticosteroid treatment was stopped. The treatment was intricate due to the concurrent bleeding and thrombotic manifestations.

Histopathological implications of Aspergillus infection in lung.

This paper opens with a discussion on the significance of invasive fungal infections in advanced contemporary medicine, with an emphasis on the intractability of disease management and the difficulties of diagnosis. This is followed by a discussion concerning classification, histopathological features, and pathophysiology. While it has been largely accepted that Aspergillus species is recognized by cellular receptors and attacked by neutrophils, the radiological and macroscopic findings linking infection with neutropenia remain unconfirmed. In an effort to gain a better understanding of the pathophysiology and pathogenesis of invasive aspergillosis, we wish to emphasize the utility of radiological and histopathological examinations since these can provide detailed information on the extremely complex interaction between the causative microbes and tissue responses. A review of noninvasive or semi-invasive aspergillosis is also provided, with particular emphasis on chronic necrotizing pulmonary aspergillosis, which is recognized as a transition form of simple pulmonary aspergilloma and invasive pulmonary aspergillosis, although few findings have been reported in this area.

Acquired hemophilia A associated with IgG4-related lung disease in a patient with autoimmune pancreatitis.

Immunoglobulin G4 (IgG4)-related lung diseases can occur in patients with autoimmune pancreatitis (AIP). However, the causal relationship between AIP and acquired hemophilia A (AH) is unknown. We herein report the first case of AH associated with IgG4-related lung disease that developed in a patient with AIP. A 65-year-old asymptomatic man with a history of AIP and sclerosing cholangitis diagnosed at the age of 57 was admitted to our hospital due to an abnormal reticulonodular shadow on chest X-ray. An examination of lung biopsy specimens revealed IgG4-positive plasma cell infiltration in the interstitium. The serum IgG4 level was elevated. One year later, the patient developed a progressive severe hematoma in the left femoral muscle. On admission, laboratory examinations revealed severe anemia with a markedly prolonged activated partial prothrombin time, a decreased level of factor VIII (FVIII) activity, and the existence of anti-FVIII antibodies. These findings were consistent with a diagnosis of AH. No relapse has been observed over the past 25 months, during which time, corticosteroid therapy has been continuously administered.

[A case with an aberrant systemic arterial supply to the basal lung diagnosed by three-dimensional computed tomography and successfully treated with surgical resection of an aberrant artery].

A 21-year-old man was admitted to our hospital complaining of recurrent hemoptysis. Computed tomography revealed ground-glass opacities in the right lower lung field, and three-dimensional computed tomography (3D-CT) demonstrated an aberrant artery which originated from the descending aorta and supplied the right S10b. Bronchoscopy showed no evidence of intraluminal bleeding or bronchial branching abnormalities. The patient was given a diagnosis of aberrant systemic arterial supply to the right normal basal segment of the lung (Pryce type I). Since the affected area, supplied from an aberrant systemic artery, was very small with no abnormalities in the lung parenchyma, the patient underwent a single resection of the aberrant artery via video-assisted thoracoscopy (VATS) without segmentectomy. The patient remained free of hemoptysis during 5 months follow-up after the operation.

[Efficacy of combination therapy with bosentan and sildenafil for refractory pulmonary arterial hypertension associated with fibrotic lung in systemic sclerosis].

A 54-year-old woman with a 20-year history of Raynaud phenomenon was admitted to our hospital complaining of progressive dyspnea on exertion since 5 years previously. Interstitial lung disease was diagnosed, accompanied by pulmonary arterial hypertension (PAH) associated with systemic sclerosis. After oxygen therapy and treatment with sildenafil, her clinical condition and PAH gradually improved. However, she was readmitted due to deterioration of Raynaud phenomenon and progressive dyspnea in March 2009. Right heart catheterization findings demonstrated that her mean pulmonary arterial pressure (PAP) was elevated, at 48 mmHg. Bosentan was therefore added to an increased dose of sildenafil. Consequently, her dyspnea, 6-min walking distance, serum brain natriuretic peptide level, and PAP improved. Combination therapy with bosentan and sildenafil was effective for this case of refractory PAH associated with fibrotic lung in systemic sclerosis.

[An autopsied case of giant cell myocarditis and myositis associated with invasive thymoma].

A 75-year-old man was given a diagnosis of invasive thymoma (WHO type B3, stage IVa) in 2004. He received 8 cycles of chemotherapy with doxorubicin, vincristin, cyclophosphamide and cisplatin from November 2004 to May 2005, combined thoracic radiotherapy (total dosage 60 Gy) in April 2006, and 2 cycles of chemotherapy with carboplatin and paclitaxel from July 2008 to August 2008. He was readmitted to our hospital complaining of fever and neck pain in September 2008. Laboratory data on admission revealed elevated serum levels of CRP, GOT, GPT, LDH, CK, and troponin-I with hypo gamma-globulinemia. Although he received immunoglobulin and antibiotic therapy, he suddenly died of cardiac shock on the 9th hospital day. On postmortem examination of the myocardium, the skeletal muscles of the neck and iliopsoas muscle showed inflammatory cell infiltration containing multinucleated giant cells with degeneration and necrosis of the muscle tissues. These findings were consistent with giant cell myocarditis with polymyositis. Autopsy findings suggested that sudden death was caused by giant cell myocarditis, probably associated with invasive thymoma.