Central Bronchial Deformity in Pulmonary Sarcoidosis: A Finding Suggestive of an Upper Lobe Fibrotic Phenotype on Chest Images.

RATIONALE AND OBJECTIVES: Bronchial and lung parenchymal structural remodeling may occur due to disease progression in patients with pulmonary sarcoidosis; however, its mechanisms remain unclear. Central bronchial deformity (CBD) associated with shrinkage in the upper lobe (SUL) is often observed in such patients. This study aimed to examine the association between CBD and structural remodeling to identify features indicating disease severity on chest images. MATERIALS AND METHODS: This retrospective cohort study included 72 patients with pulmonary sarcoidosis, excluding patients with only bilateral hilar lymphadenopathy. The participants were divided into with and without CBD groups to examine the association between CBD and other structural remodeling, including SUL, cyst and/or low attenuation area-like emphysema (Cyst/LAA), pleural/sub-pleural thickening (PT), and traction bronchiectasis (TrBE), in the upper lobe on chest images. The association of CBD phenotype with respiratory dysfunction was also examined. RESULTS: CBD was highly associated with SUL (81.4% vs. 8.9%), Cyst/LAA (44.4% vs. 6.7%), and PT (59.2% vs. 3.7%). The respective odds ratios in the univariable and multivariable analyses were as follows: SUL, 45.1 and 39.9; Cyst/LAA, 11.2 and 14.2; and PT, 64.0 and 68.7. TrBE was frequently associated with CBD (22.25% vs. 4.4%); the odds ratio was 6.14 in the univariable analysis. Furthermore, participants with CBD exhibited lower %FVC and %DLCO. CONCLUSION: CBD is significantly associated with lung remodeling (SUL, Cyst/LAA, TrBE, and PT) and respiratory dysfunction. CBD may be a crucial clinical phenotype to identify upper lobe fibrotic changes.

Prognostic impact of the cross-sectional area of the erector spinae muscle in patients with pleuroparenchymal fibroelastosis.

Pleuroparenchymal fibroelastosis (PPFE) progresses slowly but sometimes relatively quickly, leading to decreased activities of daily living (ADL) and muscle weakness. Skeletal muscle atrophy and muscle weakness in chronic obstructive pulmonary disease (COPD) patients may be caused by cachexia and are associated with reduced ADLs and increased risk of death. However, the association between skeletal muscle mass and the prognosis of PPFE patients remains unknown. We retrospectively analysed the clinical significance of the cross-sectional area of the erector spinae muscle (ESMCSA), a skeletal muscle index, and predictors of mortality within 3 years in PPFE 51 patients, idiopathic pulmonary fibrosis (IPF) 52 patients and COPD 62 patients. PPFE patients had significantly lower ESMCSA than IPF or COPD patients, and lower ESMCSA (< 22.57 cm2) was associated with prognosis within 3 years (log-rank test; p = 0.006), whereas lower body mass index (BMI) showed no association. Multivariate analysis showed that ESMCSA was an independent predictor of mortality within 3 years in PPFE patients (hazard ratio, 0.854; 95% confidence interval: 0.737-0.990, p = 0.036). These results suggest the importance of monitoring ESMCSA in PPFE patients and that assessing ESMCSA in PPFE patients could be a more useful prognostic indicator than BMI.

A 33-Year-Old Man With Hemoptysis and Renal Dysfunction.

CASE PRESENTATION: A 33-year-old man presented with a 10-day history of fever, dry cough, and dyspnea. He reported small amounts of frank hemoptysis that occurred several times a day for the past 3 days and a reduction in urine volume. There was no joint pain, skin rash, muscle weakness, or bleeding symptoms, except for the hemoptysis. He had a medical history of childhood asthma and untreated hypertension for the past 2 years. He had no history of smoking, recent travel, medication use, or occupational inhalation.

Paradoxical Formation of a Pleuroparenchymal Fibroelastosis-like Lesion in the Chronic Course of Pulmonary Sarcoidosis.

We herein report the long-term changes in chest computed tomography (CT) findings from early sarcoidosis lesions to pleuroparenchymal fibroelastosis (PPFE)-like lesions in a 30-year-old man with granulomas on a transbronchial lung biopsy. Multiple bilateral micronodular and nodular opacities around the bronchovascular bundle in the upper lobes detected by chest CT in 2004 disappeared, but paradoxically, peripheral consolidations continued to grow at the periphery of the original lesions. Chest CT in 2017 confirmed the progression of bilateral shrinkage of the upper lobe, spread of peripheral consolidations and wedge-shaped opacities below the first rib, and bronchiectatic air bronchograms, confirming PPFE-like lesions.

Honeycomb-like structures in sarcoidosis pathologically showing granulomas in walls of clustered bronchioles.

In the clinical setting, it is often difficult to judge whether honeycomb-like structures represent progression of fibrosis in pulmonary sarcoidosis or a complication by interstitial pneumonitis. This report described a valuable case in which pathology of video-assisted thoracoscopic surgery specimens collected from the lungs with honeycomb-like structures that were continuous with the dilated bronchioles on chest computed tomography (CT) showed granulomas in the membranous bronchiole walls, thereby demonstrating that the honeycomb-like structures were lung lesions of sarcoidosis. Pathological features of these structures on chest CT included cystic changes attributable to incorporation of peripheral alveoli into dilated bronchioles in lobules: these findings in lung sarcoidosis were different from those corresponding to honeycomb lung in idiopathic pulmonary fibrosis/usual interstitial pneumonia. Radiological and pathological findings showed the possibility that progressive clustering of dilated bronchi and bronchioles causes cystic changes, resulting in the formation of honeycomb-like structures as fibrosis progresses in sarcoidosis with lung involvement.

Computed Tomography Images of Fibrotic Pulmonary Sarcoidosis Leading to Chronic Respiratory Failure.

BACKGROUND: There is currently no consensus on the morphology of severe fibrotic pulmonary sarcoidosis, and we examined computed tomography (CT) findings and progression. METHODS: We analyzed findings in 10 consecutive patients (three men, seven women) with pulmonary sarcoidosis requiring oxygen therapy for chronic respiratory failure, who were extracted from >2500 sarcoidosis patients (three hospitals, 2000-2018). Patients with comorbidities causing chronic respiratory failure were excluded. RESULTS: Predominant findings were consolidations along the bronchovascular bundles comprising 'central-peripheral band', traction bronchiectasis, peripheral cysts/bullae, and upper lobe shrinkage. Traction bronchiectasis arose from opacities comprising 'central-peripheral band'. Clustering of traction bronchiectasis at the distal side formed honeycomb lung-like structures in three patients. Upper lobe shrinkage progressed in seven patients together with progression of consolidations, 'central-peripheral band', traction bronchiectasis clusters, and cysts, while patients without shrinkage included two patients with severe multiple cysts without traction bronchiectasis. Restrictive ventilatory impairment developed in most patients. Pulmonary hypertension (PH) was detected radiologically in five patients, and chronic progressive pulmonary aspergillosis (CPPA) in four patients. CONCLUSIONS: During progression, consolidations comprising 'central-peripheral band' progressed together with traction bronchiectasis clusters and peripheral cysts, resulting in upper lobe shrinkage. This may lead to respiratory failure with possible complications such as PH and CPPA.

Usefulness of low-dose methotrexate monotherapy for treating sarcoidosis.

OBJECTIVE: Methotrexate (MTX) is a cytotoxic agent that is commonly employed as an alternative to corticosteroids to treat sarcoidosis, although the proper use and efficacy of MTX as a single agent remain unclear. METHODS: The clinical records of patients newly diagnosed with sarcoidosis who were admitted to our institution between 2000 and 2009 were reviewed. Among these patients, 26 received 7.5 mg of MTX per week as a single agent, and the independent effects of MTX were analyzed. RESULTS: Six of the 26 patients (23%) exhibited an improvement of sarcoidosis-related lesions. The skin lesions demonstrated a relatively higher response rate (37%) than the pulmonary lesions (9%). Ten of the 26 patients (39%) experienced adverse effects, mostly mild hepatotoxicity. No severe adverse effects, including irreversible hepatotoxicity, were observed. CONCLUSION: Although the efficacy of low-dose MTX monotherapy for sarcoidosis in this study was not high (23%), some patients exhibited definite improvements, and the drug proved to be safe, suggesting its possible benefits as a single agent for treating sarcoidosis.

Respiratory bronchiolitis and lung carcinoma.

BACKGROUND: Cigarette smoking is the primary causative factor for lung carcinoma and respiratory bronchiolitis (RB), particularly RB-associated interstitial lung disease (RB-ILD). However, the link between lung cancer and RB/RB-ILD remains undefined. We examined whether pathological fibrosis lesions exist simultaneously in patients with lung carcinoma because the fibrous lesions could be precancerous. METHODS: Clinical, radiological, and pathological features were consecutively evaluated in 67 current smokers, 22 ex-smokers, and 35 nonsmokers who underwent surgical resection for lung carcinoma. The presence of interstitial changes was evaluated by high-resolution computed tomography (HRCT). The pathological examination focused on RB, RB with fibrosis, and coexistent interstitial changes. RESULTS: RB with fibrosis was observed in 13/67 current smokers with centrilobular nodular and/or patchy ground-glass opacities patterns or emphysema on HRCT. RB without fibrosis was observed in 12/67 current smokers with a centrilobular pattern, emphysema, or a normal pattern on HRCT. The Brinkman smoking index was significantly higher in the RB with fibrosis group (1278±133) than in the RB without fibrosis group (791±131). No RB with/without fibrosis features were noted in nonsmokers or ex-smokers. Squamous cell carcinoma was observed in 11/13 patients with RB with fibrosis, whereas adenocarcinoma was observed in 7/12 patients with RB without fibrosis. CONCLUSIONS: Squamous cell carcinoma located in peripheral areas was primarily observed in patients with RB with fibrosis, whereas adenocarcinoma was primarily observed in patients with RB without fibrosis. Interstitial fibrosis with RB caused by continuous heavy cigarette smoking may increase the risk of developing squamous cell carcinoma.

Protein C deficiency in a family with thromboembolism and identified gene mutations.

Protein C is the central component of the major anti-thrombotic regulatory system, and individuals with hereditary protein C deficiency tend to have an increased risk of thromboembolism. During the last several years, mutations causing protein C deficiency have been identified. In the present study, we report familial cases with three nucleotide substitutions: One is a missense mutation Arg169Trp, which was previously reported. The other two are C-154T promoter polymorphism (rs1799808 on dbSNP database), the function of which is unknown and Ser99Ser synonymous polymorphism (rs5936). All three mutations were found in a 24-year-old patient with pulmonary thromboembolism and his 54-year-old father who also had pulmonary thromboembolism. C-154T promoter polymorphism (rs1799808 on dbSNP database) and Ser99Ser synonymous polymorphism (rs5936) were found in the patient's mother.

Obstructive sleep apnea-hypopnea syndrome patients with overweight and hypertension in a Japanese workplace.

The objective of this study was to determine the relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and overweight combined with hypertension and to examine whether OSAHS in conjunction with overweight and hypertension is associated with daytime sleepiness. In a Japanese workplace of 28,636 employees, 368 men (19-62 yr old), who were anxious regarding their OSAHS symptoms, underwent home pulse oximetry. Of these, 153 men subsequently underwent all-night polysomnography (PSG), and OSAHS was diagnosed in 149. We next classified these 149 men into the following groups: A [Overweight (-)/Hypertension (-), n=41], B [Overweight (-)/Hypertension (+), n=15], C [Overweight (+)/Hypertension (-), n=46], and D [Overweight (+)/Hypertension (+), n=47]. The Epworth Sleepiness Scale (ESS) was used to evaluate daytime sleepiness and the apnea-hypopnea index (AHI) was used to evaluate the severity of OSAHS. The averages of the ESS score and the AHI were compared in each group. Both the average ESS scores and the percentage of ESS scores > or =11 were not significantly different among the groups. The average AHI of group D was the highest among all of the groups and that of group C was significantly higher than those of groups A and B. In all the groups, the OSAHS patients with overweight and hypertension in this study had the highest AHI. The level of daytime sleepiness evaluated by the ESS in this study was almost the same in the OSAHS patients regardless of the degree of overweight or hypertension. These observations suggest that it is necessary to positively recommend PSG to men who are suspected of having OSAHS with overweight and hypertension, even if they do not have daytime sleepiness.

[Recurrence of non-small cell lung cancer after successful treatment with gefitinib--report of three cases].

Gefitinib, a first epidermal growth factor receptor (EGFR) inhibitor has been reported to be effective in chemotherapy-resistant non-small cell lung cancer. Gefitinib was also reported, however, to produce severe adverse effects, such as interstitial lung disease. Thus, clinical evaluation of gefitinib is still controversial and further studies are needed. We present 3 cases of non-small cell lung cancer (stage IV adeno-carcinoma) that showed recurrence after successful gefitinib treatment. Symptoms of all patients ameliorated in a week after the therapy, and radiograph and laboratory data improved. However, all showed recurrence in 3 to 7 months. After recurrence, patient 1 was re-treated with gefitinib at the request of the patient. Patient 2 has been on gefitinib. Patient 3 was treated with gefitinib, which was later replaced by another chemotherapy agent. After recurrence, however, no effective response was obtained in any of the 3 cases. There have been several reports of good response to gefitinib therapy at the first time in patients with advanced non-small cell lung cancer, but few reports of recurrence in patients after successful therapy with this agent. This report is thought to be important for the clinical evaluation of gefitinib and useful in terms of information about the resistance of gefitinib.

[A case of bronchostenosis in the allograft after lung transplantation in pulmonary lymphangioleiomyomatosis].

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease characterized by hamartomatous proliferation of abnormal smooth muscle cells in the lungs. Recently, severe LAM has been listed as an indicated disease for lung transplantation. A 34-yr-old woman with severe pulmonary cystic changes in a chest CT scan was diagnosed as having an isolated form of pulmonary LAM without genetic disorders. Despite intensive progesterone treatment, her pulmonary functions deteriorated rapidly. In January 2001, a left single-lung transplantation was performed from a cadaveric donor. The total operating time was 8 hours and 47 minutes. Total ischemic time was 5 hours and 59 minutes, which was within the permitted time limit. Except for right pneumothorax, the postoperative course was fairly good without any sign of rejection or infection in the allograft. For about two months after transplantation, bronchostenosis occurred in the left lower lobe bronchus, and necessitated a stent placement. During the following three months, stenosis of the bronchi in the anastomotic and peripheral sites occurred repeatedly, which also necessitated stent placement or balloon dilations on each occasion. Despite all the intensive treatment, the bronchostenosis of the peripheral sites still remains and improvement of her pulmonary functions has been poor. Moreover, a recent chest CT scan revealed a progression of the disease in the native lung. Consequently, we registered her as a candidate for transplantation of the right lung. Bronchostenosis should be kept in mind as a complication of lung transplantation.