Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its frequent adverse effects are manageable, including gastrointestinal symptoms, peripheral neuropathy, and ...thrombocytopenia. Severe lung toxicity has not previously been reported. Between June 2004 and September 2005, 13 Japanese patients with multiple myeloma were treated with bortezomib in Toranomon Hospital, Juntendo University School of Medicine, and Jichi Medical School. Four of them developed severe pulmonary complications, and 2 died of respiratory failure without progression of underlying disease. To our knowledge, this is the first report on life-threatening pulmonary adverse effects after bortezomib therapy. Previous clinical studies on bortezomib, mostly in the United States and Europe, have shown low incidences of pulmonary adverse effects. Our study suggests that bortezomib can cause serious lung injury, and that its incidence might vary among different ethnicities. Clinicians need to be alert to the possibility.
A 68-year-old Japanese woman with asthma of recent onset and a long history of membranous glomerulonephropathy (MN) was admitted because of multifocal pulmonary infiltrates, marked eosinophilia, mild ...renal dysfunction, a rash on her feet, and right median nerve paralysis. Although MPO- and PR3-ANCA were negative, skin biopsy demonstrated leukocytoclastic vasculitis and Churg-Strauss Syndrome (CSS) was diagnosed. She also had salivary gland swelling and a high serum IgG4 level. Renal biopsy revealed MN with eosinophil-rich tubulointerstitial nephropathy. Her symptoms resolved after the start of corticosteroid therapy. The present case shows that ANCA-negative CSS can have a clinical condition similar to IgG4-related kidney disease.
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.
Background
Since 1996, transcatheter renal artery embolization (renal TAE) has been performed to reduce the volume of the kidneys in patients with autosomal dominant polycystic kidney disease (ADPKD) ...and complications of nephromegaly at our hospital. Respiratory dysfunction is often a serious problem in these patients before TAE.
Patients and methods
Between January 2006 and October 2008, renal TAE was performed and lung function testing percent vital capacity (%VC) and percent forced expiratory volume in 1 s (%FEV
1.0
) was done by spirometry in 28 patients on maintenance hemodialysis who had respiratory symptoms.
Results
Renal volume was 6,330.5 ± 3,126.5 cm
3
(range 1,771–12,761 cm
3
) before TAE, and decreased significantly to 2,892.2 ± 1,841.7 cm
3
(range 622–6,961 cm
3
) by 12 months after TAE (
p
= 0.0001). The percent decrease of renal volume at 12 months after TAE versus baseline was 45.6 ± 14.6% (range 6.6–67.3%). %VC showed a significant increase from 95.9 ± 14.8% (range 63–127%) before renal TAE to 100.1 ± 11.7% (range 78–120%) at 12 months after TAE (
p
< 0.01). %FEV
1.0
was also significantly increased from 87.9 ± 15.0% (range 55–110%) before renal TAE to 92.5 ± 14.4% (range 58.0–115.0%) at 12 months after TAE (
p
< 0.01). The changes of VC (ΔVC%) and FEV
1.0
(ΔFEV
1.0
%) both showed a significant positive correlation with the reduction of renal volume (Δ renal volume) (
p
= 0.001 and
p
= 0.004, respectively).
Conclusion
Since TAE not only led to a significant decrease of renal volume in ADPKD patients with nephromegaly, but also improved lung function (both %VC and %FEV
1.0
), pulmonary dysfunction should be recognized as one of the extrarenal complications of ADPKD.
Cardiac metastasis from lung cancer is rarely diagnosed antemortem, as it usually causes no symptoms or signs. We report the case of a 56-year-old man with recurrent lung adenocarcinoma in whom ...developed a large mass in the ventricular septum, complete atrioventricular block, and obstruction of the left ventricular outflow tract.
The rising incidence of pulmonary aspergillosis is a major clinical concern. However, only a limited number of antifungal drugs are available in Japan that are effective for pulmonary Aspergillus ...infections. Micafungin (MCFG), a newly developed echinocandin family antifungal drug, has potent antifungal activity in vitro, but few reports detailing its clinical effectiveness have been published to date. A retrospective study was performed using data from nine patients (seven males and two females) with chronic invasive forms of pulmonary aspergillosis, who were treated with either MCFG alone or together with other antifungal drugs between April 2003 and March 2004. The overall efficacy of the treatments was evaluated in the terms of clinical, mycological, serological and radiological responses. The average age of the patients was 61.9 (20-83) years old. Four patients received only MCFG and the remaining five patients were treated with MCFG in combination with amphotericin B (AMB) only (1 patient), itraconazole (ITC) only (2 patients) or AMB backed up by ITC during AMB discontinuation periods (2 patients). The mean duration of MCFG administration was 59.2 (28-96) days. Overall, the treatment was judged to have been effective for seven of nine patients. No patient's condition deteriorated in response to treatment. Administration of MCFG alone was judged to have been effective in three of four patients. No notable adverse effects were documented during MCFG administration. These data suggest that MCFG may be an effective and safe antifungal drug for the treatment of chronic invasive forms of pulmonary aspergillosis.
The progressive airway obliteration caused by obliterative bronchiolitis (OB) has been widely noted in the world. In contrast, the obstructive respiratory disorder caused by diffuse panbronchiolitis ...(DPB) has been reported mainly from Japan. Therefore, there might be a considerable overlap between OB and DPB in Japan.
To clarify the clinicopathological similarities as well as the differences between OB and DPB, 15 patients with OB and 6 patients with DPB were evaluated clinicopathologically.
The underlying disorders in OB were graft-versus-host disease (GVHD) in 7, rheumatoid arthritis in 3, Kartagener's syndrome in 2, and polymyositis/dermatomyositis, non-tuberculous mycobacterial disease and mycoplasmal pneumonia in one each. The lung pathology demonstrated that the primary obstructive lesions were in the membranous bronchioli in OB. In contrast, they were confined to the respiratory bronchioli in DPB. In addition, OB was classified into two major morphologic types, namely, constrictive and cellular. Clinical manifestations included cough and/or dyspnea in 13 with OB and in 6 with DPB, chronic parasinusitis in 3 with cellular OB and in 6 with DPB. The pulmonary function tests revealed obstructive impairments in all patients with OB and DPB. The chest CT images showed small centrilobular nodules in 64% of those with OB and in all with DPB. The prognosis of constrictive OB was worse than that of cellular OB and DPB.
This study demonstrated that histopathologically marked differences existed between OB and DPB, although striking similarities in clinical manifestations were also noted in both diseases.
Bronchorrhea in patients with bronchioloalveolar carcinoma is not uncommon. However, to our knowledge, an effective treatment for bronchorrhea in these patients has not been established. Recently, we ...have confirmed the efficacy of inhaled indomethacin in severe refractory bronchorrhea in comparison to that of other medications in two patients with bronchioloalveolar carcinoma. Despite the administration of a macrolide and corticosteroid, sputum volume increased to 700 mL/d in case 1 and to 200 mL/d in case 2 and hypoxemia and dyspnea deteriorated. Within a few days after the initiation of treatment with inhaled nebulized indomethacin (75 mg/d), sputum volume started to decrease and was controlled to < 100 mL/d, associated with alleviation of dyspnea and hypoxemia. To our knowledge, this is the first report of successfully treated refractory bronchorrhea associated with bronchioloalveolar carcinoma by inhaled indomethacin, resulting in markedly reduced sputum volume, improved quality of life, and prolonged survival.
There is a scarcity of reports comparing gender differences in polysomnographic findings among Asian patients with sleep apnea (SA). In this study, we elucidated gender differences in the clinical ...features and polysomnographic findings of SA patients in Japan.
We conducted a case-matched control study to compare the gender differences. A total of 4,714 patients (4,127 men; 587 women) were matched for age, apnea-hypopnea index (AHI), and body mass index (BMI). The criteria used for sex matching were (I) age ±4 years, (II) AHI ± 4 h of sleep, and (III) BMI ±2 kg/m(2). This facilitated the comparison of polysomnography sleep variables in 296 men and 296 women with SA.
Compared with their male counterparts, female SA patients had a significantly higher rapid eye movement AHI men: 27.7 (IQR, 14.3-45.2); women: 43.3 (IQR, 25.5-56.6); P<0.001, lower supine AHI men: 29.7 (IQR, 16.8-49.5); women: 25.0 (IQR, 14.7-39.3); P=0.004, longer total sleep time (TST), and non-rapid eye movement (NREM) sleep stage 3 (N3), %TST TST in men: 356.3 (IQR, 319.5-392.3); women: 372.0 (IQR, 327.8-404.5); P=0.007; N3, %TST in men: 8.8 (IQR, 3.0-14.6); women: 14.4 (IQR, 8.3-20.4); P<0.001, and better sleep efficiency men: 80.9 (IQR, 71.0-88.0); women: 83.2 (IQR, 74.5-90.0); P=0.011.
This study revealed that women with SA had a significantly longer TST and N3, %TST, which represents deep sleep. Future prospective studies must be conducted together with polysomnography tests including electromyography of pharyngeal muscle expansion and electroencephalography.
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