Ryuichi Takenaka

Successful treatment with tacrolimus of progressive interstitial pneumonia associated with amyopathic dermatomyositis refractory to cyclosporine

A 58-year-old male was admitted to our hospital because of periungual nailfold an erythema and erythematous rash on the dorsal joints of his hands and feet, but no muscle weakness. He was thus diagnosed to have amyopathic dermatomyositis. He had moderate hypoxemia and his chest computed tomography scans demonstrated bilateral ground-glass opacities, implicating complication with interstitial pneumonia. Therapy was initiated with pulsed methylprednisolone followed by high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine. The skin manifestations improved; however, the pulmonary infiltrates and hypoxemia deteriorated during the 2-month period of the treatment. The treatment was switched from cyclosporine to tacrolimus because of an inadequate clinical response to the therapy, and this resulted in the resolution of interstitial pneumonia. This case indicates that tacrolimus administration should be considered for patients with this life-threatening disorder when it is judged to be refractory to cyclosporine.

Asthma and Sinusitis: Association and Implication

Background: Sinusitis occurs frequently in asthmatic patients. Epidemiologic data on sinusitis and lower airway disease must be evaluated with caution because they are based mostly on symptoms and do not include nasal endoscopic or computed tomography (CT) findings. Clinical support and evidence for this association are lacking. We evaluated the impact of sinusitis on lower airway disease in patients with well-characterized asthma. Methods: Subjects (n = 188) completed a questionnaire designed to provide information about their signs and symptoms related to asthma, allergic rhinitis (AR) and sinus disease. Patients (n = 104) were divided into four groups based on the presence or absence of sinusitis and/or AR. Clinical findings were compared in asthma patients with and without diagnosed sinusitis, by an otorhinolaryngologist or based on sinus CT findings. Results: The prevalence of sinusitis in patients with asthma was 36.7%. Sinus CT scan abnormalities were detected in 66.3% of patients with asthma. The scans revealed abnormal opacity in 17.9% of asthmatic patients without a history of sinusitis. There was a significant correlation between the rate of asthma severity and sinus morphologic abnormalities in patients with and without sinusitis. In adult-onset asthma (≧16 years old), sinusitis frequently preceded asthma, whereas in non-adult-onset asthma (<16 years old) it preceded sinusitis. The complication rate of sinusitis in asthmatic patients was significantly higher in adult-onset asthma than in non-adult-onset asthma. Conclusions: Our findings suggest that bronchial asthma is closely related to sinusitis and the onset age of asthma is important when considering allergic disease frequency. Whether sinus disease directly affects the intensity of bronchial inflammation remains to be elucidated.

Links between bronchial asthma and allergic rhinitis in the Oita Prefecture, Japan.

Recent studies have strengthened the concept that bronchial asthma and allergic rhinitis are manifestations of an inflammatory process within a continuous airway. This study was performed to compare clinical findings in asthma with or without rhinitis in Japan. Nasal symptoms were present in 99.6% of asthma patients. The prevalence of allergic rhinitis in patients with asthma was 52.4%. Bronchial asthma attacks in one third of patients with rhinitis were coincident with worsening of nasal symptoms. In adults (> 16 years of age), rhinitis frequently preceded asthma, whereas asthma preceded rhinitis in children (< 16 years of age). The frequency of rhinitis in asthma decreases with increasing age. This study demonstrated a clear link between upper and lower airway disorders in Japan.

Increased serum ADAM8 concentration in patients with drug-induced eosinophilic pneumonia-ADAM8 expression depends on a the allergen route of entry

BACKGROUND ADAM8 (a disintegrin and a metalloprotease 8) has been linked to asthma and eosinophilic pneumonia (EP). ADAM8 cleaves a variety of substrates and is a sheddase for CD23, the low affinity IgE receptor. The concentration of soluble ADAM8 (sADAM8) is increased in bronchoalveolar lavage fluid (BALF) from patients with smoking-induced acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP), but not drug-induced EP (Drug-EP). In AEP, the BALF sADAM8 concentration significantly correlates with the soluble CD23 concentration (sCD23). METHODS To evaluate the involvement of ADAM8 in the pathogenesis of eosinophilic pneumonia, we measured the concentrations of sADAM8 and its substrate, soluble CD23 (sCD23), in serum from patients with AEP, CEP, and Drug-EP. We also measured the change in the sADAM8 concentration after a provocation test. RESULTS In contrast to the BALF findings, serum sADAM8 concentrations were increased in Drug-EP (mean+/-SEM; 639.6+/-49.15) and serum ADAM8 levels correlated positively with the serum sCD23 levels in patients with Drug-EP (P=0.0080, R(2)=0.8465). Serum sADAM8 concentrations were also increased in AEP (409+/-76.91) and CEP (644.7+/-87.03). Serum ADAM8 concentrations were also elevated after the provocation test. CONCLUSION Serum ADAM8 concentrations were elevated in Drug-EP, although the sADAM8 concentrations were not increased in the BALF in Drug-EP. Thus, the pathogenesis of AEP and Drug-EP may be distinct with regard to allergen exposure; AEP may be caused by the inhalation of antigens, whereas Drug-EP may be caused by bloodstream antigens. These findings indicate that ADAM8 levels reflect the route of eosinophilic inflammation in EP.

Influence of age on symptoms and laboratory findings at presentation in patients with influenza-associated pneumonia.

Influenza virus infection is a major respiratory infectious disease that generally induces pneumonia. The clinical manifestations of influenza virus infection and community-acquired pneumonia (CAP) differ between elderly persons and younger adults. To determine the clinical features of influenza-associated pneumonia, we studied 21 adult patients with influenza-associated pneumonia, as indicated by positive test results for influenza virus antigen. At presentation, the higher-age patients (> or =75 years; n=12) with influenza-associated pneumonia had lower body temperature than did the lower-age (<75 years) patients (n=9). Conversely, the laboratory data indicated significantly higher C-reactive protein (CRP) concentration in higher-age patients than that in lower-age patients. None of the 18 patients undergoing neuraminidase inhibitor therapy died, but two of three patients who did not receive this therapy died from complications of advanced pneumonia. In this study, vaccination did not appear to be an important factor for prevention of pneumonia. High-age patients with CAP have lower body temperature, raising the possibility that diagnosis and treatment may be delayed in these patients. Increased CRP levels in these patients at presentation, however, could contribute to early detection of this serious pulmonary complication.

Elevated concentrations of CCR7 ligands in patients with eosinophilic pneumonia.

Previous studies suggest that dendritic cells and macrophages play an important role in inflammation of eosinophilic pneumonia. The mechanism of dendritic cell and macrophage accumulation into the lung, however, is unknown. Here, we hypothesized that CCR7 ligands, CCL19 and CCL21, contribute to the accumulation of dendritic cells and alveolar macrophages in the inflamed lung of patients with eosinophilic pneumonia.

The use of frequency scale for the symptoms of GERD in assessment of gastro-oesophageal reflex symptoms in asthma

In adult asthmatics the incidence of gastro-oesophageal reflux disease (GERD) reportedly ranges from 34% to 89%. Oesophageal pH monitoring and endoscopy are not required in the patient with typical GERD symptoms before the initiation of a therapeutic trial. Diagnosis of GERD on the basis of history is the simplest and quickest method, placing no demand on patients. Recently, a new questionnaire (FSSG; Frequency Scale for the Symptoms of GERD) was produced to evaluate the severity and the therapeutic response of GERD. The FSSG (F-scale) was used to assess the GERD in subjects with persistent moderate to severe asthma treated with anti-inflammatory asthma medication. In the present study, 27.4% of the patients with asthma had symptoms suggestive of GERD. There is significant correlation between GERD symptom (F-scale score) and severity of cough and sputum. The observations suggested that reflux symptoms, not gastric dysmotility symptoms, significantly associated with severity of cough, not of sputum. It is the first such study to use a FSSG as incidence of GERD symptoms in asthmatics and examine the relationship between F-scale score and asthmatic symptoms.

Amoxicillin-Induced Eosinophilic Pneumonia with Granulomatous Reaction: Discrepancy between Drug-Induced Lymphocyte Stimulation Test Findings and the Provocation Drug Test

A 59-year-old man was admitted to the hospital with pulmonary infiltration, fever, erythema, and eosinophilia. Two weeks before admission, he received amoxicillin, acetaminophen, and shoseiryu-to (a Japanese herbal medicine) for a common cold. Bronchoalveolar lavage was performed, and an increased number of eosinophils was recovered. Transbronchial biopsy specimens showed granuloma and interstitial thickening with eosinophils and lymphocytes. Drug-induced eosinophilic pneumonia was suspected, so all drugs were discontinued. The symptoms and infiltration shadow disappeared. A drug-induced lymphocyte stimulation test (DLST) was positive for acetaminophen but not for amoxicillin. In contrast to the DLST, a provocation test revealed that amoxicillin induced the drug allergy. A very striking observation was the coexistence of pulmonary eosinophilia and granulomatous lung infiltrations. In addition, there was a discrepancy between the DLST and provocation test findings. To our knowledge, there is no previous report of drug-induced eosinophilic pneumonia with a granulomatous reaction.

Elevated Concentrations of Liver-Expressed Chemokine/CC Chemokine Ligand 16 in Bronchoalveolar Lavage Fluid from Patients with Eosinophilic Pneumonia

Background: Eosinophilic pneumonia is characterized by the prominent accumulation of eosinophils and lymphocytes in the lung parenchyma. Liver-expressed chemokine (LEC)/CC chemokine ligand 16 (CCL16) is a novel functional ligand for H4 which is expressed on eosinophils and also an affinity ligand for CCR1, CCR2, CCR5 and CCR8 which are expressed on T lymphocytes and monocytes. The purpose of this study is to clarify the role of LEC/CCL16 in eosinophilic pneumonia. Methods: The LEC/CCL16 level was measuredusing an enzyme-linked immunosorbent assay in the bronchoalveolar lavage fluid (BALF) of 33 patients with eosinophilic pneumonia, 26 patients with sarcoidosis and 10 healthy volunteers. The cell sources of LEC/CCL16 in BALF were evaluated by immunocytochemistry. Results: The LEC/CCL16 levels in BALF from patients with eosinophilic pneumonia were significantly higher than those from patients with sarcoidosis and healthy volunteers. The BALF LEC/CCL16 levels correlated with the numbers of BALF eosinophils and lymphocytes, respectively. The BALF LEC/CCL16 levels were significantly decreased after remission in eosinophilic pneumonia. In immunocytochemistry, the LEC/CCL16 expression was clearly observed in CD1a-positive dendritic cells as well as in CD68-positive macrophages harvested from patients with eosinophilic pneumonia, but not from the controls. Conclusions: These results suggest that LEC/CCL16 produced by dendritic cells as well as by alveolar macrophages contributes to the accumulation of eosinophils and lymphocytes into the inflamed lungs of patients with eosinophilic pneumonia.

Chromobacterium haemolyticum Pneumonia Possibly Due to the Aspiration of Runoff Water

Here, we report a case of pneumonia possibly caused by the aspiration of runoff water containing Chromobacterium haemolyticum. A 69-year-old man became intoxicated with alcohol, fell into a ditch, and lost consciousness after suffering a blow to the head. The lower half of his body was completely paralyzed because of damage to his spinal cord, and he aspirated runoff water from the ditch. Chest computed tomography scans revealed consolidation in the right upper lobe and bilateral lower lobes. A sputum culture detected gram-negative bacteria that was identified as C. haemolyticum. Antibacterial chemotherapy was initiated, and the clinical course was favorable. To the best of our knowledge, this is the first report of C. haemolyticum pneumonia in the literature.