Tomoshige Wakayama

Cough variant and cough-predominant asthma are major causes of persistent cough: a multicenter study in Japan

Abstract Objective: Persistent cough is a frequent cause of doctor and hospital visits, and its incidence may be increasing. However, diagnosis of the cause of cough remains difficult. Because different causes of cough have different treatments, accurate diagnosis of the cause of cough is critical. To gain a better understanding of the causes of cough in Japan, we performed a multicenter epidemiological study of Japanese patients. Methods: The study involved seven institutions in five different areas of Japan, and was conducted over 1 year from March 2009. Patients aged ≥16 years attending the participating centers for the first time complaining of cough persisting for ≥3 weeks were eligible. Patients with chest X-ray abnormalities responsible for cough, fever or blood-stained sputum were excluded, while those with wheeze or shortness of breath were included. Frequency and severity of cough were assessed using questionnaires, and laboratory tests were performed to enable differential diagnoses. Results: Among the 313 patients evaluated, mean duration of cough symptoms was 192.1 ± 558.4 days. Cough variant asthma (CVA) was the most common cause of prolonged/chronic cough (42.2%), followed by cough-predominant asthma (CPA) (28.4%), atopic cough (7.3%) and chronic obstructive pulmonary disease (6.7%). Patients with an unclear diagnosis were treated with tulobuterol, a transdermal β2-agonist preparation, for 1–2 weeks. Transdermal tulobuterol improved assessments of cough in patients with CVA or CPA, enabling rapid diagnosis of these diseases. Conclusions: These findings show that CVA and CPA are the main causes of cough persisting for ≥3 weeks.

A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis

Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10-30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and β2-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of β2-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.

Effect of Thrombomodulin Alfa on Disseminated Intravascular Coagulation in Patients with Lung Cancer

Objective The mortality rate due to disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in those without. We examined the effect of treatment with thrombomodulin alfa (TM-α) for DIC in lung cancer patients. Methods Subjects were 57 patients with DIC (43 men, 14 women; mean age, 71.7 years), comprising 31 with lung cancer and 26 without. DIC patients with or without lung cancer did not differ significantly in their background characteristics. Results No significant difference was noted in the mortality rate between patients with lung cancer (61.3%) and those without (57.7%). However, the dose of TM-α was higher for survivors with lung cancer than for non-survivors (473.1 U/kg/day vs. 380.6 U/kg/day; p<0.01). Although no significant difference was noted in the DIC score between these four groups, the serum C-reactive protein level (6.9 mg/dL vs. 11.6 mg/dL; p<0.05) and prothrombin time-international normalized ratio (PT-INR; 1.10 vs. 1.52; p<0.05) were lower in survivors with lung cancer than in the non-survivors with lung cancer. The initial body temperature in non-survivors without lung cancer was lower than that in survivors without lung cancer (37.2℃ vs. 37.9℃, p<0.01), and the platelet count and the time to recovery from DIC in patients without lung cancer showed a significant negative correlation (r2=0.438, p<0.05). Conclusion Our findings suggest that although 380 U/kg/day of TM-α is the recommended dose for DIC treatment, a higher dose may reduce the mortality rate of lung cancer patients with DIC. Furthermore, TM-α should be initiated before worsening of DIC parameters.

Molecular biological analysis in a patient with multiple lung adenocarcinomas: Molecular analysis in lung ADC

The utility of molecular biological analysis in lung adenocarcinoma has been demonstrated. Herein we report a rare case presenting as multiple lung adenocarcinomas with four different EGFR gene mutations detected in three lung tumors. After opacification was detected by routine chest X‐ray, the patient, a 64‐year‐old woman, underwent chest computed tomography which revealed a right lung segment S4 ground‐glass nodule (GGN). Follow‐up computed tomography revealed a 42 mm GGN nodule with a 26 mm nodule (S6) and a 20 mm GGN (S10). Histopathology of resected specimens from the right middle and lower lobes revealed all three nodules were adenocarcinomas. Four EGFR mutations were detected; no three tumors had the same mutations. Molecular biological analysis is a promising tool for the diagnosis of primary tumors in patients with multiple lung carcinomas of the same histotype, enabling appropriate treatment.

Risk factors for disseminated intravascular coagulation in patients with lung cancer: Risk factors for DIC with lung cancer

The mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non‐lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer.

Survey on the proper use of an adrenaline auto-injector in 551 Japanese outdoor workers after Hymenoptera stings

Sex Men 1179 (96.6) Women 29 (2.4) Unknown 12 (1.0) Age (years) 10e19 13 (1.1) 20e29 125 (10.2) 30e39 307 (25.2) 40e49 320 (26.2) 50e59 250 (20.5) 60e69 174 (14.3) 70 27 (2.2) Unknown 4 (0.3) Questionnaire 1: A Hymenoptera sting after prescription of an adrenaline autoinjector Yes 551 (45.2) No 662 (54.3) Unknown 7 (0.6) 2: Systemic reaction after a Hymenoptera stingy Yes 65 (11.8) No 475 (86.2) Unknown 11 (2.0) 3: Use of an adrenaline auto-injector after a Hymenoptera stingy Yes 46 (8.3) No 503 (91.3) Unknown 2 (0.4) 4: Hospital visit immediately after use of an adrenaline auto-injectorz Yes 39 (84.8) No 6 (13.0) Unknown 1 (2.2) 5: Re-prescription of an adrenaline auto-injector Yes 701 (57.5) No 146 (12.0) First prescription, before expiration day 356 (29.2)