Yasushi Yamamoto

Resistin Is Closely Related to Systemic Inflammation in Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA) is closely related to systemic inflammation. Resistin is an adipocyte-derived cytokine (adipokine) that may link obesity with inflammation. Objective: We aimed to investigate whether incremental changes in OSA severity, from normal to severe, primarily affect the levels of resistin and other adipokines. Methods: Serum levels of resistin, interleukin-6 (IL-6) and leptin were examined in 31 men with OSA and 10 men without OSA, matched for age, body mass index (BMI) and several metabolic profiles. In 11 of the 31 men with OSA, these mediators were reexamined after 3 months of nasal continuous airway pressure (nCPAP) therapy. Results: Levels of resistin and IL-6 were simultaneously elevated in men with OSA compared with those in men without OSA (p < 0.05), while levels of leptin did not differ. The resistin and IL-6 levels tended to increase with increasing disease severity (p < 0.05), which was based on the apnea-hypopnea index (AHI). The average oxyhemoglobin saturation during sleep (p < 0.01) and IL-6 (p < 0.05) emerged as significant determinants of resistin, even after adjustments for age, BMI, leptin levels and metabolic risk factors. After nCPAP therapy, the elevated levels of resistin and IL-6 decreased, reaching almost baseline levels of controls. Before treatment, AHI correlated positively with the reduction rate in resistin (p < 0.05). Conclusion: In OSA patients, resistin production can be enhanced by hypoxic stress during sleep, possibly mediating systemic inflammatory processes. nCPAP therapy may play a beneficial role in the control of resistin production.

Increased serum level of vascular endothelial growth factor in Mycobacterium avium complex infection.

Objective:  Pulmonary infection caused by Mycobacterium avium complex (MAC) is one of the granulomatous diseases which are associated with the expression of vascular endothelial growth factor (VEGF). The aim of the present study was to clarify the association of VEGF with the pathogenesis of MAC infection.

Minimal Change Nephrotic Syndrome Associated with Gefitinib and a Successful Switch to Erlotinib

Minimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome (NS). We herein present the case of a 57-year-old woman with advanced lung adenocarcinoma treated with the tyrosine kinase inhibitor (TKI) gefitinib who developed NS. A renal biopsy revealed minor glomerular abnormalities, and the patients symptoms improved exclusively with the discontinuation of gefitinib. Therefore, we diagnosed her with MCNS associated with gefitinib treatment. A few months later, however, she developed recurrent lung tumors. Following the challenging initiation of the TKI erlotinib, she achieved remission without proteinuria. We thus conclude that erlotinib is a potential treatment option in patients with NS associated with gefitinib therapy.

Primary Mediastinal Amyloidosis Diagnosed by Transbronchial Needle Aspiration

A 61-year-old woman was referred for an evaluation of mediastinal lymphadenopathy (arrowheads indicate mediastinal lymph nodes) (Picture 1). Some of the nodes had partial calcification. Hilar lymphadenopathy and diffuse interstitial changes in the lungs were absent. Positron emission tomography revealed an uptake of F-fluorodeoxyglucose in the mediastinum (Picture 2). A histological analysis using endobronchial ultrasound-guided transbronchial needle aspi-

Histamine H1 antagonist levocetirizine as a potential cause of lung injury

Histamine H1 antagonists rarely cause drug‐induced lung injury (DLI). A woman in her 60s, who had been taking antihistaminic levocetirizine for 2 months, presented with progressive cough and shortness of breath. A chest radiograph showed patchy infiltrations on both lower lung fields. Chest computed tomography findings were consistent with non‐specific interstitial pneumonia. Serum markers associated with interstitial pneumonias were elevated. Room air arterial blood gas analysis revealed hypoxemia. Restrictive ventilatory impairment was noted with reduced diffusing capacity. Transbronchial lung biopsy specimens demonstrated unclassifiable alveolitis. Steroid pulse therapy was introduced for respiratory distress, but the initial response to treatment was poor. A drug lymphocyte stimulation test was positive for levocetirizine. The interstitial pneumonia improved following withdrawal of levocetirizine. Her illness has not recurred under steroid therapy and the discontinuation of levocetirizine. Antihistaminics may have a potential risk of DLI.

Interstitial lung disease associated with human papillomavirus vaccination

Vaccinations against the human papillomavirus (HPV) have been recommended for the prevention of cervical cancer. HPV-16/18 AS04-adjuvanted vaccines (Cervarix) are said to have favourable safety profiles. Interstitial lung diseases (ILDs) can occur following exposure to a drug or a biological agent. We report a case of ILD associated with a Cervarix vaccination. A woman in her 40s, with a history of conisation, received three inoculations of Cervarix. Three months later, she presented with a cough and shortness of breath. Findings from a computed tomography of the chest and a transbronchial lung biopsy were consistent with non-specific interstitial pneumonia. Workup eliminated all other causes of the ILD, except for the vaccination. Over the 11 months of the follow-up period, her symptoms resolved without steroid therapy. The onset and spontaneous resolution of the ILD showed a chronological association with the HPV vaccination. The semi-quantitative algorithm revealed that the likelihood of an adverse drug reaction to Cervarix was “Probable”. The outcome was relatively good, but more attention should be paid to a potential risk for HPV vaccinations to cause ILDs. Wherever possible, chest radiographic examinations should be performed in order not to overlook any ILDs.

Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report

BackgroundImmune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab.Case presentationA 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other examinations. After treatment, steroid reactivity was poor.ConclusionThis is the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab-induced irAE. Clinicians should be aware of this kind of potential neurological complication by using immune check point inhibitor and start the treatment of this irAE as soon as possible.

Contents Vol. 76, 2008

I. Adcock, London H.D. Becker, Heidelberg D. Bouros, Athens N.S. Cherniack, Newark, N.J. K.F. Chung, London V. Cottin, Lyon C. Dooms, Leuven S. Gasparini, Ancona P.M. Gustafsson, Göteborg J. Hammer, Basel C. Kroegel, Jena F. Kummer, Vienna P.N. Mathur, Indianapolis, Ind. L.P. Nicod, Lausanne T. Nishino, Chiba M. Noppen, Brussels D. Olivieri, Parma C.P. Page, London E.W. Russi, Zürich J. Vansteenkiste, Leuven Editorial Board