COPD assessment test as a possible tool for evaluating health-related quality of life in lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease that causes an obstructive ventilatory impairment similar to chronic obstructive pulmonary disease (COPD) and impairs the health-related quality of life (HRQoL). Here, we extended the use of the COPD assessment test (CAT) to patients with chronic respiratory diseases other than COPD. Specifically, the CAT was administered to patients with LAM for the first time. METHODS: Using data from 25 patients with LAM at Juntendo University who participated in the Multicenter Lymphangioleiomyomatosis Sirolimus Trial for Safety (MLSTS), we evaluated changes in pulmonary function, responses to HRQoL questionnaires (the CAT, St. George׳s Respiratory Questionnaire [SGRQ], EuroQOL Visual Analogue Scale [EuroQOL-VAS], and Functional Performance Inventory [FPI]), and the association between pulmonary function and HRQoL during a 24-month period of sirolimus treatment. RESULTS: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and CAT total scores improved over the 24 months of sirolimus treatment (5.33 ± 1.20 ml/month, 2.61 ± 1.16 ml/month, and -0.127 ± 0.022 score/month, respectively), whereas SGRQ total score, EuroQOL-VAS score, and FPI score did not. Most pulmonary functions at baseline were associated with the CAT breathlessness score during the first year. Longitudinal changes in FEV1, FEV1%predicted, or FEV1/FVC correlated significantly with the scores of CAT total, CAT breathlessness, and SGRQ activity. When analyzed by stepwise multivariate regression within a linear mixed-effects model, CAT breathlessness and confidence scores were significantly associated with a change in FEV1 from the baseline value (P = 0.0011, and P = 0.0441). CONCLUSION: Our results suggest that the CAT is a useful instrument for assessing HRQoL in sirolimus-treated patients with LAM.

Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.

This report describes two patients with sporadic lymphangioleiomyomatosis complicated by protein-losing enteropathy (PLE). Imaging studies indicated retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one patient; whereas the site in the other patient was intestinal. Treatment with sirolimus led to the complete resolution of PLE within several months; additionally, marked shrinkage was observed in the lymphangioleiomyomas of both cases. These findings suggest that colonic or intestinal lymphatic congestion due to neighboring lymphangioleiomyomas was the mechanism for the development of PLE. At the time of writing this report, the beneficial effect of sirolimus has lasted for more than 3 years.

Impact of Airflow Limitation on Comorbidities and Postoperative Complications in Patients Undergoing Thoracic Surgery: A Retrospective Observational Study.

PURPOSE: To assess the frequency of airflow limitation (AFL), and the relationship between AFL and preoperative comorbidities or postoperative complications in patients who had undergone thoracic surgery. METHODS: The medical records of patients who underwent non-cardiac thoracic surgery at our institution between August 1996 and January 2013 were retrospectively reviewed. On the basis of preoperative pulmonary function tests, patients were classified with those with FEV1/FVC <70% [AFL(+) group] or with FEV1/FVC ≥70% [AFL(-) group]. Patient characteristics, preoperative comorbidities and postoperative complications were compared between the groups. RESULTS: Of the 3667 patients assessed, 738 (20.1%) were allocated to the AFL(+) group. AFL was an independent risk factor for three preoperative comorbidities: chronic obstructive pulmonary disease (odds ratio [OR]: 4.65), bronchial asthma (OR 4.30) and cardiac diseases (OR 1.41). Airflow limitation was also an independent risk factor for postoperative respiratory failure including long-term oxygen therapy (OR 2.14) and atelectasis (OR 1.90) in the patients who underwent lobectomy or partial resection of the lung. CONCLUSIONS: Our retrospective study revealed that careful attention needs to be paid to airflow limitation in patients who undergo non-cardiac thoracic surgery since it appears to be an important feature of preoperative comorbidities and to increase postoperative complications.

Effects of transdermal tulobuterol on dyspnea and respiratory function during exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Poor exercise tolerability is a major barrier to improving the quality of life of patients with chronic obstructive pulmonary disease (COPD). Although COPD is often treated with long-acting ß2 adrenergic agonists, few studies have examined their effects on exercise tolerability. METHODS: In this study, Japanese COPD patients were treated with 2 mg transdermal tulobuterol, a long-acting ß2 agonist, once daily for 4 weeks. Spirometry and exercise tests were conducted at baseline and at the end of treatment. The patients conducted constant load (30 W for 5 min) and incremental load (starting at 10 W and increasing by 10 W every 1 min for 5 min to a maximum load of 50 W) exercise tests on a cycle ergometer. RESULTS: Thirteen patients with stable COPD participated in this study (mean age ± standard deviation (SD), 69.5±9.7 years; smoking history 55.9±27.8 pack-years). Resting spirometric parameters were unchanged at the end of treatment. The maximum Borg scale for dyspnea and the Borg scale slope (BSS) decreased significantly from baseline to the end of treatment. The threshold load of dyspnea (TLD) increased slightly, although not significantly, in the constant load test but not in the incremental load test. There were no changes in respiratory parameters during exercise after treatment. CONCLUSIONS: In conclusion, we found that treatment with transdermal tulobuterol for 4 weeks improved self-assessed dyspnea in Japanese COPD patients during constant and incremental exercise tests. This improvement in dyspnea may encourage patients to perform daily life activities or regular physical activity.

Do respiratory comorbidities limit the diagnostic usefulness of ultrasound-guided needle aspiration for subpleural lesions?

BACKGROUND: The usefulness of ultrasound-guided needle aspiration for subpleural lesions has been reported. However, no reports have evaluated its usefulness and safety in patients with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and interstitial pneumonia (IP), which can increase the risk of iatrogenic pneumothorax. In this study, we evaluated the influence of chronic respiratory diseases (CRDs) on the usefulness and safety of ultrasound-guided needle aspiration for subpleural lesions. METHODS: Between January 2000 and September 2011, we examined 144 patients with intrapulmonary subpleural lesions. We retrospectively reviewed clinical data, including lesion size on thoracic computed tomography (CT), ultrasound findings, pathological findings obtained by ultrasound-guided needle aspiration, final diagnosis, and complications. RESULTS: A positive definitive diagnosis was obtained in 74.3% of all 144 patients; 84.7% patients with malignant diseases, including lung cancer; and 26.9% patients with benign diseases. Of the 144 patients, 64 belonged to the CRD group and 80 to the non-CRD group. The former included 31 patients with COPD, six with emphysematous changes on thoracic CT, 17 with IP, and 10 with other diseases. The positive rate of diagnosis for malignant diseases was 84.7% in the CRD group, which was the same as that in the non-CRD group. With regard to complications related to ultrasound-guided aspiration, there were only two cases of pneumothorax in the CRD group and one in the non-CRD group. CONCLUSION: Ultrasound-guided aspiration is safe and useful for subpleural lesions, particularly malignant lesions, even in patients with respiratory comorbidities such as COPD and IP.

Solitary fibrous tumor of the pleura: ultrasonographic imaging findings of 3 cases.

Solitary fibrous tumor (SFT) of the pleura is a rare tumor of mesenchymal origin. Although radiographic findings of thoracic computed tomography and magnetic resonance imaging in the evaluation of SFTs of the pleura have been documented, the value of ultrasonography is uncertain. We presented the ultrasonographic findings of 3 pathologically proven cases of SFTs arising from the visceral pleura. In all the cases, thoracic ultrasonography demonstrated homogeneous, hypoechoic, hemicycle, extrapulmonary lesions, which showed respiratory movement with the adjacent lung, consistent with pedunculated tumors. Preoperative thoracic ultrasonography could be useful in the evaluation of patients with pleural tumors, especially SFTs.

Prevalence and clinical features of lymphedema in patients with lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease predominantly affecting young women. Some of these patients develop lymphedema of the lower extremities and buttocks; however, neither the exact frequency of LAM-associated lymphedema nor the clinical features of such patients is well delineated. OBJECTIVES: To document the frequency, features, and treatment of LAM-associated lymphedema. METHODS: We reviewed all medical records of patients listed in the Juntendo University LAM registry for the 30 years preceding August 2010. RESULTS: Of 228 patients registered with a diagnosis of LAM, eight (3.5%) had LAM-associated lymphedema of the lower extremities. All were females with sporadic LAM, and their mean age when diagnosed was 32.5 years (range 23-44). Lymphedema of the lower extremities was the chief or a prominent presenting feature in five of these LAM patients. CT scans showed that all eight patients had enlarged lymph nodes (lymphangioleiomyomas) in the retroperitoneum and/or pelvic cavity. Yet, cystic destruction of the lungs was mild in four patients, moderate in two and severe only in two. Seven of these patients were treated by administering a fat-restricted diet and complex decongestive physiotherapy, and four received a gonadotropin-releasing hormone analog. With this combined protocol, all eight patients benefitted from complete relief or good control of the lymphedema. CONCLUSIONS: Lymphedema is a rare complication of LAM and may be associated with axial lymphatic involvement or dysfunction rather than severe cystic lung destruction. The combined multimodal treatments used here effectively resolved or controlled LAM-associated lymphedema.

Pulmonary rehabilitation program including respiratory conditioning for chronic obstructive pulmonary disease (COPD): Improved hyperinflation and expiratory flow during tidal breathing.

BACKGROUND: Pulmonary rehabilitation has generally relieved symptoms, strengthened exercise endurance and improved health-related quality of life (QOL) in patients with COPD, but recovery of pulmonary function remains questionable. This analysis of our innovative rehabilitation program is directed at documenting changes in patients' expiratory airflow limitation, pulmonary symptoms and QOL. This program is designed to provide "respiratory conditioning", a physical therapist-assisted intensive flexibility training that focuses on stretching and rib cage mobilization. METHODS: Thirty-one patients with COPD who attended rehabilitation sessions at Juntendo University Hospital from 1999 to 2006 were analyzed. Pulmonary function, expiratory flow limitation during tidal breathing, six minute walk distance (6MWD), respiratory muscle strength, and St. George Respiratory Questionnaire (SGRQ) were measured before and after pulmonary rehabilitation. RESULTS: In participants ages 68±7 years, the FEV(1)% predicted was 39.3±15.7%. 6MWD, SGRQ and respiratory muscle strength were significantly improved after pulmonary rehabilitation. Although neither FEV(1)% predicted nor FEV(1)/FVC was affected to a significant extent, indicating little effect on airflow limitation, expiratory flow limitation in supine as well as seated during tidal breathing improved significantly. Moreover, rehabilitation significantly diminished TLC% predicted, FRC% predicted, RV% predicted and RV/TLC values, thus indicating a reduction of hyperinflation of the lungs at rest. CONCLUSIONS: The present results suggest that our rehabilitation program with respiratory conditioning significantly lowered the hyperinflation of lungs at rest as well as the expiratory flow limitation during tidal breathing. In patients with COPD, overall pulmonary function improved, exercise endurance increased and health-related QOL was enhanced.

Breakthrough lung Scedosporium prolificans infection with multiple cavity lesions in a patient receiving voriconazole for probable invasive aspergillosis associated with monoclonal gammopathy of undetermined significance (MGUS).

Breakthrough non- Aspergillus mold infections among patients receiving the anti-mold azole antifungal agents like voriconazole or posaconazole have been increasingly reported. We report a case of lung Scedosporium prolificans infection with multiple cavities in a 58-year-old man with monoclonal gammopathy of undetermined significance (MGUS) during voriconazole treatment for probable invasive aspergillosis. Cultures of repeated sputum specimens yielded the same fungus until his death 83 days after diagnosis. S. prolificans should be considered in patients with breakthrough infections receiving voriconazole.

[A case of pulmonary metastases from bladder cancer, suspected of recurrent Wegener's granulomatosis].

A 26-year-old-woman was given a diagnosis of Wegener's granulomatosis and began treatment by both prednisolone and cyclophosphamide at another institution. She was then admitted to our hospital due to progressive multiple pulmonary nodules. A diagnosis of pulmonary metastases from bladder cancer was established with radiological and histological examinations obtained by transbronchial lung biopsy (TBLB) and transurethral resection of the bladder tumor (TUR-Bt). She had already received a total dose of 120 g of cyclophosphamide, which could be related to the development of bladder cancer. On detecting multiple pulmonary nodules in patients with Wegener's granulomatosis treated with cyclophosphamide, it is necessary to consider the possibility of pulmonary metastases form urinary bladder cancer.

Malignant pleurisy associated with primary lung cancer well controlled by pleurodesis using distilled water.

The patient was an 84-year-old man patient diagnosed as malignant pleurisy associated with lung cancer. After drainage of the right pleural effusion, pleurodesis with distilled water was performed. Despite the enlargement of the primary lesion of the lung cancer during the follow-up period, the amount of pleural effusion did not increase for more than one year. No adverse effects associated with pleurodesis were noted. Pleurodesis with distilled water should be considered as one of the choices for treatment in the management of malignant pleurisy especially in elderly.

An autopsy case of subacute cor pulmonale due to pulmonary tumor cell emboli in a patient with gastric cancer.

A 53-year-old woman was admitted to our hospital due to a severe respiratory condition and malnutrition. Radiological and electrophysiological findings suggested the existence of inexplicable cor pulmonale. Although we commenced to determine the causes of her severe condition, she suddenly died 3 days after admission. Postmortem autopsy revealed tumor cell microemboli in the small pulmonary arteries due to gastric cancer. Such a case of cor pulmonale as the first clinical manifestation is exceptionally rare. Occult malignancy should be considered as a differential diagnosis when one encounters a patient with subacutely aggravated respiratory condition and inexplicable cor pulmonale.

Refractory recurrent thymoma successfully treated with long-acting somatostatin analogue and prednisolone.

The patient was 54-year-old woman diagnosed as recurrent invasive thymoma (type B3; WHO classification). Although partial response was obtained by systemic chemotherapy (PAC: cisplatin, doxorubicin, cyclophosphamide), the tumor started to become enlarged after cessation of chemotherapy. Combined treatment of octreotide and prednisolone was administrated because various chemotherapies, including PAC, were not effective. After seven months, the tumor size was markedly decreased. The combination of octreotide and prednisolone should be considered as one of the choices of treatment in patients with recurrent thymoma.

[Evaluation of clinical effectiveness of Pazufloxacin Mesilate in acute exacerbation of chronic respiratory diseases].

Patients with chronic respiratory disease have increased susceptibility to infection, because of impairment of the local immunologic defense mechanism in the airway system, which often results in acute exacerbation. Acute exacerbation of chronic respiratory disease is one of the most important predictors of increased morbidity and mortality, and thus the management in the acute phase is essential for better prognosis. Although the clinical guidelines for the management of respiratory tract infections published by the Japanese Respiratory Society recommend administering fluoroquinolones intravenously in case of hospitalized patients, the clinical evidence is still limited. In this study, we evaluated the efficacy of Pazufloxacin Mesilate (PZFX). an intravenous fluoroquinolone. in patients with chronic respiratory diseases complicated with acute exacerbation caused by acute respiratory infections. As a result, 16 out of 18 cases were successfully treated with PZFX. No adverse event was observed during this study. These results may support the validity of administering intravenous fluoroquinolone in hospitalized patients with acute exacerbation caused by infections, as recommended by the Japanese Respiratory Society.

[Spirometry and other pulmonary function tests for the screening and evaluation of patients with chronic obstructive pulmonary disease (COPD)].

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible. The existence of airflow limitation can be determined by spirometry that measures the forced expiratory volume in one second (FEV1) and its ratio (FEV1/FVC) to the forced vital capacity (FVC). Airflow limitation is defined as FEV1 /FVC<70% after the inhalation of short-acting bronchodilator. In addition, FEV1% predicted, a ratio of FEV1 to the predicted value determined by age, gender and height, is utilized to define the severity degree of COPD. Some of the other pulmonary function tests are useful for understanding the pathophysiology of COPD. These tests include the diffusing capacity measurement of carbon monoxide per liter of alveolar volume (DLco/VA), measurement of lung volume using the nitrogen washout technique and whole body plethysmography, and measurement of lung compliance.

[Measurement of diffusing capacity by the intrabreath method].

The diffusing capacity of the lung for carbon monoxide (DLco) is usually measured by the single breath method with a 10-second breath hold. With the introduction of rapid gas analyzers, an alternative method for measurement of DLco, the intrabreath method, has been developed. The intrabreath method does not depend upon length of time or other conditions during either breath holding or expiration. The aim of this study was to compare the single breath method and intrabreath method of DLco measurement. DLco measured by the intrabreath method (DLco IB) was compared with DLco measured by the single breath method (DLco SB) in 32 normal subjects, 88 patients with obstructive impairment and 39 patients with restrictive impairment. DLco SB could not be measured in 2 patients with obstructive impairment and 7 patients with restrictive impairment, while in all except one patient with severe restrictive impairment, DLco IB was able to be measured. There was an excellent correlation between DLco IB and DLco SB in normal subjects (rho = 0.942, p < 0.0001). There was no difference in the mean value between DLco IB (21.0 +/- 5.4 ml/min/mmHg) and DLco SB (20.9 +/- 4.9 ml/min/mmHg). In the obstructive impairment group there was also an excellent correlation between DLco IB and DLco SB (rho = 0.922, p < 0.0001). In the mild or moderate obstructive impairment group (%FEV1 > 50%), no difference between DLco IB (11.8 +/- 5.80 ml/min/mmHg) and DLco SB (12.4 +/- 4.68 ml/min/mmHg) was found. In the severe obstructive impairment group (%FEV1 < 50%), the DLco IB (7.29 +/- 3.61 ml/min/mmHg) was lower than the DLco SB (8.58 +/- 3.24 ml/min/mmHg) (p < 0.0001). The relation between DLco SB and DLco IB was equally strong in patients with restrictive impairment (rho = 0.742, p < 0.0001). There was an excellent correlation between DLco IB and DLco SB in normal subjects, the obstructive impairment group and the restrictive impairment group. The intrabreath method therefore seems to be a useful and reliable alternative to the single breath method for clinical measurement of DLco.