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Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.

The pathology of coronavirus disease 2019 (COVID-19) is exacerbated by the progression of thrombosis, and disseminated intravascular coagulation (DIC), and cytokine storms. The most frequently reported coagulation/fibrinolytic abnormality in COVID-19 is the increase in D-dimer, and its relationship with prognosis has been discussed. However, limits exist to the utility of evaluation by D-dimer alone. In addition, since the coagulation/fibrinolytic condition sometimes fluctuates within a short period of time, regular examinations in recognition of the significance of the examination are desirable. The pathophysiology of disseminated intravascular coagulation (DIC) associated with COVID-19 is very different from that of septic DIC, and both thrombotic and hemorrhagic pathologies should be noted. COVID-19 thrombosis includes macro- and microthrombosis, with diagnosis of the latter depending on markers of coagulation and fibrinolysis. Treatment of COVID-19 is classified into antiviral treatment, cytokine storm treatment, and thrombosis treatment. Rather than providing uniform treatment, the treatment method most suitable for the severity and stage should be selected. Combination therapy with heparin and nafamostat is expected to develop in the future. Fibrinolytic therapy and adsorption therapy require further study.

This study was conducted in order to identify imaging features on three-dimensional computed tomography (CT) of unexplained chronic cough (UCC) patients with positive sputum cultures for filamentous Basidiomycetes (f-BM). UCC outpatients who had been given various questionnaires for cough, pulmonary function tests, and fungal cultures of sputum were evaluated. Multidetector row CT (MDCT) was performed for three-dimensional CT analysis of the lungs. Retrospective analysis was carried out with three groups: f-BM culture-positive group, other fungal culture-positive group, and culture-negative group. The Kruskal–Wallis test, analysis of variance, Fischer exact test, χ2 test, Student’s t test, Mann–Whitney U test, Spearman’s correlation coefficient, and Dunn–Bonferroni post hoc method were used for statistical analysis. Of the 50 patients, 3 were excluded and the remaining 47 were included in the analysis. There were no significant differences in respiratory function or clinical characteristics among the three groups. The common features on high-resolution CT (HRCT) included tree-in-bud (TIB) pattern, multiple centrilobular nodules, and bronchial wall thickening. Bronchiolar mucus plugs were detected in 7 (15%) of 47 cases. Bronchiole wall thickness and %FEV1 appeared to be slightly correlated (p = 0.033, r = 0.357). The bronchiole walls were significantly thicker when mucus plugs were found (p = 0.010). Bronchiolar walls were the thickest and the score of mucus plugs was the highest in patients with f-BM culture-positive sputum (p = 0.008). Imaging findings for identifying f-BM culture-positive fungus-associated chronic cough (FACC) patients include high mucus plug scores and bronchiolar wall thickening on three-dimensional CT. • Three-dimensional computed tomography helps clinicians assess patients with unexplained chronic cough and identify those with fungus-associated chronic cough. • A retrospective single-center study showed that computed tomography images in patients with filamentous Basidiomycetes cultured from sputum had mucus plugs and bronchiolar wall thickening. • UCC patients with sputum cultures positive for filamentous Basidiomycetes may have fine airway lesions that could not be detected without three-dimensional computed tomography.

Lipoprotein diacylglyceryl transferase (Lgt) catalyzes the first step in the biogenesis of Gram-negative bacterial lipoproteins which play crucial roles in bacterial growth and pathogenesis. We demonstrate that Lgt depletion in a clinical uropathogenic Escherichia coli strain leads to permeabilization of the outer membrane and increased sensitivity to serum killing and antibiotics. Importantly, we identify G2824 as the first-described Lgt inhibitor that potently inhibits Lgt biochemical activity in vitro and is bactericidal against wild-type Acinetobacter baumannii and E. coli strains. While deletion of a gene encoding a major outer membrane lipoprotein, lpp, leads to rescue of bacterial growth after genetic depletion or pharmacologic inhibition of the downstream type II signal peptidase, LspA, no such rescue of growth is detected after Lgt depletion or treatment with G2824. Inhibition of Lgt does not lead to significant accumulation of peptidoglycan-linked Lpp in the inner membrane. Our data validate Lgt as a novel antibacterial target and suggest that, unlike downstream steps in lipoprotein biosynthesis and transport, inhibition of Lgt may not be sensitive to one of the most common resistance mechanisms that invalidate inhibitors of bacterial lipoprotein biosynthesis and transport. IMPORTANCE As the emerging threat of multidrug-resistant (MDR) bacteria continues to increase, no new classes of antibiotics have been discovered in the last 50 years. While previous attempts to inhibit the lipoprotein biosynthetic (LspA) or transport (LolCDE) pathways have been made, most efforts have been hindered by the emergence of a common mechanism leading to resistance, namely, the deletion of the gene encoding a major Gram-negative outer membrane lipoprotein lpp. Our unexpected finding that inhibition of Lgt is not susceptible to lpp deletion-mediated resistance uncovers the complexity of bacterial lipoprotein biogenesis and the corresponding enzymes involved in this essential outer membrane biogenesis pathway and potentially points to new antibacterial targets in this pathway.

Lipoprotein diacylglyceryl transferase (Lgt) catalyzes the first step in the biogenesis of Gram-negative bacterial lipoproteins which play crucial roles in bacterial growth and pathogenesis. We demonstrate that Lgt depletion in a clinical uropathogenicEscherichia colistrain leads to permeabilization of the outer membrane and increased sensitivity to serum killing and antibiotics. Importantly, we identify the first ever described Lgt inhibitors that potently inhibit Lgt biochemical activityin vitroand are bactericidal against wild-typeAcinetobacter baumanniiandE. colistrains. Unlike inhibition of other steps in lipoprotein biosynthesis, deletion of the major outer membrane lipoprotein,lpp, is not sufficient to rescue growth after Lgt depletion or provide resistance to Lgt inhibitors. Our data validate Lgt as a novel druggable antibacterial target and suggest that inhibition of Lgt may not be sensitive to one of the most common resistance mechanisms that invalidate inhibitors of downstream steps of bacterial lipoprotein biosynthesis and transport.

The high mortality rate due to severe Herpes simplex viral (HSV) hepatitis is associated with the difficulty of its diagnosis. We describe the extremely rapid disease course of a patient who died of severe HSV hepatitis. A 73-year-old woman was admitted for a bronchial asthma attack. Her symptoms improved with steroid treatment, but she developed a sore throat and painful swallowing. On day 12 after admission, she suddenly went into shock. Blood test results showed a significant increase in the liver enzyme levels, with remarkable disseminated intravascular coagulation. She died the same day. The autopsy revealed extensive coagulative necrosis of the liver. Viral inclusion of type A Cowdry bodies was found in the residual hepatocytes in the hepatic lobule. Immunostaining revealed HSV type 1 positivity. We diagnosed the cause of death as severe HSV hepatitis. On examination of a stored serum sample, the patient tested positive for the HSV immunoglobulin (Ig)-M antibody, and the HSV RNA level was very high (1 × 109 copies/mL). Remarkably, the HSV IgG test result was negative, and we diagnosed her as having had an initial HSV infection. Hepatitis due to HSV is very rare in healthy adults; however, there are many reports of immune-deficient cases. The presence of HSV IgG is decreasing in the elderly population because of the change in living environments/lifestyles. The increasing use of immunosuppressive drugs, such as steroids, for treating diseases in elderly patients could be linked to the increased prevalence of initial HSV infections, resulting in liver injury.

Background: Filamentous basidiomycetes (f-BMs) are involved in some unexplained chronic cough (UCC) cases that can be improved by the administration of antifungal agents. The disease concept was termed fungus-associated chronic cough (FACC). The current diagnostic criteria warrant environmental fungi isolation from respiratory specimens, which is hardly conceivable for such fungi. Objectives: This study aimed to detect the f-BMs Bjerkandera adusta, the most common pathogen in FACC, from respiratory specimens of patients with UCC using real-time polymerase chain reaction (PCR). It also evaluated the applicability of the PCR system to detect antifungal agent responders among patients with unexplained cough. Methods: The PCR system specific to B. adusta was developed and its utility was evaluated using sputum samples from 23 patients with chronic cough. Results: B. adusta was detected in 10 out of 14 patients with UCC (71.4%), in contrast to only 2 out of 9 patients with non-UCC (22.2%; p < 0.05 with the Fisher’s exact test). The copy number of the samples correlated with the therapeutic impact score for cough symptoms following the oral administration of itraconazole. Conclusion: Development of the real-time PCR system enabled us to demonstrate that many patients with UCC might be influenced by B. adusta, a fact evidenced by the improvement of symptoms with itraconazole administration in most PCR-positive patients. This method would help in detecting itraconazole responders among patients with UCC when the isolation of f-BMs is not achievable.

Objective To compare the acute effects of single nebulized amphotericin B and budesonide in treating cough-related laryngeal sensations in chronic cough patients, a randomized, single-blind, placebo-controlled, parallel-group trial was performed between two groups with positive and negative results of basidiomycetous (BM) fungi in their sputum culture. Methods Forty patients presenting with chronic cough lasting 8 weeks or longer, whose sputum could be obtained, were recruited for this study. At the first visit, all patients underwent fungal culture sampling of sputum, capsaicin cough inhalation test, pulmonary function tests, and cough-related laryngeal sensation questionnaire (C-LSQ) consisting of 6 items with a severity scale of 0–5 for each item: (1) a sensation of irritation in the throat (SIT); (2) tickle in the throat; (3) throat clearing; (4) urge to cough; (5) a sensation of something stuck in the throat; and (6) a sensation of mucus in the throat (SMIT). The patients were randomly assigned to receive either nebulizer inhalation of 2.5 mg of amphotericin B (Group A) or nebulizer inhalation of 0.5 mg of budesonide (Group B). The efficacies of each therapy were estimated by the change in C-LSQ score. Results There were significant differences in the delta score of item 1 (SIT) and item 2 in the BM-negative group and item 6 (SMIT) in the BM-positive group at 60 min after inhalation between Groups A and B (P Conclusion The results of this study suggested that appropriate use of single inhalation of budesonide or amphotericin B, which would be selected based on the results of sputum culture, may lead to suppression of cough-related laryngeal sensations, such as SIT or SMIT.

With regard to fungal colonization and fungal sensitization, the goals of fungus-associated asthma management are as follows: 1) to survey fungi colonizing the airways of patients repeatedly; 2) to evaluate the tendency of the colonizing fungi to sensitize patients and the influence on clinical manifestations of asthma; 3) to follow disease development to allergic bronchopulmonary mycosis or sinobronchial allergic mycosis; and 4) to determine whether fungal eradication from the airway of patients is beneficial from the viewpoints of future risk factors. Recent developments in molecular biological analyses have facilitated the identification of basidiomycetous fungi that were not previously thought to be of concern in fungal allergy. The total control of fungus-associated asthma will be accomplished by environmental management established from the viewpoint of both the ecology and life cycle of the responsible fungi.

Chronic cough is a common symptom at outpatient care. An uncontrollable cough with difficulty in treatment is called chronic idiopathic cough. Recent reports have demonstrated that the presence of basidiomycetous fungi in sputum is an important clinical finding that assists in clarifying the cause of chronic cough in some cases. Research has suggested that Bjerkandera adusta is related to fungus-associated chronic cough (FACC). FACC is defined as a chronic cough associated with basidiomycetous fungi found in induced sputum and can be treated with antifungal medication. B. adusta is one of the basidiomycetous fungi that exist in cosmopolitan environments. The aim of this study was to develop a B. adusta detection method using polymerase chain reaction (PCR) with a specific primer set and to research the incidence of B. adusta in FACC. The new method successfully detected B. adusta from FACC patients. The incidence of B. adusta in FACC was 42.86 %. Antifungal drugs were effective in most cases. Significant differences in treatment duration between B. adusta patients and non-B. adusta patients were observed. It is therefore suggested that the presence of B. adusta may be one of the allergic intractable factors of chronic cough. This finding may provide identifiable differences in clinical manifestations between B. adusta and non-B. adusta in FACC and lead to possible differing remedies to treat the two forms. PCR can specifically detect B. adusta from patients suffering from chronic cough and provides a new diagnosis for FACC associated with B. adusta.

Anti-Tn-antigen monoclonal antibody MLS128 has affinity for three consecutive Tn-antigens (Tn3) more than Tn2. The major aim of this study was to isolate genes encoding MLS128 variable domains to produce a large quantity of recombinant MLS128 antibodies, in turn, allowing the conduct of studies on precise interactions between Tn3- or Tn2-epitopes and MLS128. This study describes cloning of the variable region genes of MLS128, construction of the variable region genes in single-chain variable fragments (scFv) and two scFvs conjugated with human IgG(1) hinge and Fc regions (scFv-Fc) types, and their respective expression in bacterial and mammalian cell. MLS128 scFv protein with the expected specificity and affinity was successfully prepared from inclusion bodies accumulating in Escherichia coli. Construction, expression and purification of two types of MLS128-scFv-Fc proteins with differing linker lengths in Chinese hamster ovary cells demonstrated that the purified scFv-Fc proteins had binding activity specific to the glycoprotein-expressing Tn-antigen clusters. These results revealed that VL and VH genes cloned from the hybridoma represent those of MLS128 and that recombinant antibodies produced from these genes should provide sufficient amounts of binding domains for use in 3D structural studies such as NMR and X-ray analysis.

Background: Although mucoid impaction of the bronchi (MIB) is a well-known manifestation in allergic bronchopulmonary mycosis (ABPM), when unknown samples or plural eumycetes are cultured from bronchial materials, several problems are encountered which can affect the definitive diagnostic process or successful treatment. Case Summary: The definitive diagnostic process of two patients [a 58-(Case 1) and a 70-(Case 2) year-old female] with MIB was: 1) to identify the existence of any allergic respiratory disorder, 2) to detect the fungi obtained from bronchial materials, with use of the 28S rDNA sequencing and analysis, 3) to investigate whether the detected fungus was a probable etiologic antigen, and 4) to make the final diagnosis based on the results of the inhalation examinations using the antigenic solution of the fungi. As a treatment strategy, bronchial toilet and low dose itraconazole therapy were planned according to the clinical manifestations of each patient. Discussion: The two patients with MIB were successfully diagnosed as ABPM caused by Schizophyllum commune (Sc-ABPM) accompanied with hyperattenuating mucoid impaction. The reliability of some allergological makers as a substitution for the bronchoprovocation test should be clarified in near future. Clinical manifestations demonstrated in our cases suggested that the allergic reaction such as eosinophilic bronchoalveolitis spreading around the mucus plug was a primary lesion underlying the Sc-ABPM. The success of the treatment for Sc-ABPM will be achieved by the strategy targeting to fundamental condition and by the control of the disease recurrence by means of effective environmental management.

– “Atopic cough” is a new clinical entity that presents with isolated chronic bronchodilator-resistant cough accepted in the Japanese Respiratory Society Guidelines for Management of Cough. The essential features are eosinophilic tracheobronchitis, increased cough reflex sensitivity and an atopic constitution. It has been suggested that activated helper Tlymphocytes and the cytokines which are produced by these cells are involved in the pathogenesis, but the relationship between helper T cell-derived cytokines and the airway cough reflex sensitivity remains unknown. – The effect of an orally active Th2 cytokine inhibitor, suplatast tosilate (CAS 94055-76-2, IPD™; 300 mg/day), on the cough response to inhaled capsaicin (CAS 404-86-4) was examined in ten patients with atopic cough. The capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The serum total immunoglobulin E (IgE) level and the peripheral blood eosinophil count were also determined after treatment with suplatast tosilate. – The cough threshold measured after four weeks of treatment with suplatast tosilate was significantly increased compared to the value obtained with placebo, along with a decrease of the serum IgE level and peripheral eosinophil count. – Th2 cytokines may increase the airway cough reflex sensitivity in patients with atopic cough. Oral administration of suplatast tosilate may be a novel therapy for atopic cough.

Background: The sensitization and exposure to fungal allergens have been reported to be associated with asthma. The aim of this study was to clarify the impact of sensitization to Schizophyllum commune (S. commune) on the severity and exacerbations of asthma. Methods: Ninety-two patients with asthma of various levels of severity [mild (n = 18), moderate (28), and severe (46)] and exacerbation severity [moderate (n = 43) and severe (6)] were retrospectively examined with regard to fungal sensitization such as specific IgE or intradermal skin reactions against S. commune and other common allergens. We also classified the patients into three groups: (1) three or more asthma attacks during the past year (F-BA) (n = 29),(2) one or two asthma attacks (NF-BA) (n = 20), and (3) no asthma attack (C-BA) (n = 43). Results: The positive rate of late cutaneous reactions to S. commune was higher in patients with severe asthma (41.2%) than with moderate (26.1%) or mild asthma (6.7%), and was significantly different among the three groups (P < 0.05). Although the ratio did not show a significant difference between the patients with severe (83.3%) or moderate (36.1%) exacerbation, it was higher in F-BA (60.9%) than in NF-BA (21.1%) and C-BA patients (10.0%), and it was significantly different among the three groups (P = 0.0002). Multivariate analysis identified positive results for late-phase skin reactions to S. commune and the age of the patients as an independent determinant of asthma severity, and the skin results and %FVC an independent determinant of exacerbation frequency. Conclusion: This study demonstrated that S. commune is an environmental fungus that appears to enhance both the severity of asthma and the exacerbation frequency. © 2011 Springer Science+Business Media, LLC.

Background: There is a close link between fungal sensitization and asthma severity. Although Schizophyllum commune (S. commune, "suehirotake" in Japanese), one of the basidiomycetous (BM) fungi, is a fungus that can cause allergic bronchopulmonary mycosis (ABPM) and allergic fungal sinusitis (AFS), whether the fungus causes or sensitizes subjects to asthma is unclear. Methods: The bronchial provocation test using S. commune antigen was performed in two asthmatics who had demonstrated positive skin reactions to the S. commune antigen, and low dose of itraconazole (50 mg/day) was prescribed as an adjunctive therapy for 2 weeks. The allergological features and clinical manifestations of these patients are herein evaluated and discussed. Results: Case 1 was a 71-year-old female, and case 2 was a 69-year-old male. Both patients demonstrated positive reactions to the inhalation test. A diagnosis of AFS or ABPM was excluded in both patients because of the lack of a history of pulmonary infiltrates, central bronchiectasis, a history of expectoration of brown plugs or flecks, or sinusoidal findings. Although the efficacy of itraconazole in our cases was unclear, the elevated titer of the specific IgG-for S. commune in case 2 gradually decreased during the period of antifungal therapy. Conclusions: The two patients described herein were diagnosed to have bronchial asthma caused by S. commune; so-called Schizophyllum asthma. S. commune may also be a causative fungal antigen of bronchial asthma. © 2011 Elsevier Ltd. All rights reserved.

This report describes about development of wooden panels rahmen construction that considers construction of site. The development policy was assumed to be composed of a light material, high strength and high rigidity, and long span beam.Developing excellent rahmen construction in construction on the site became possible by composing the rahmen engine frame of the wooden panel. It was confirmed that wooden panels rahmen construction had an enough rigidity for a horizontal and vertical load. And it confirmed it by the experiment.

金沢大学医薬保健研究域医学系, We herein report a case of sinobronchial allergic mycosis (SAM) caused by basidiomycetous (BM) fungi (probably Phanerochaete velutina). The patient with bronchial asthma that accompanied allergic fungal sinusitis (AFS) fulfilled all 6 criteria for diagnosing SAM. In this case, the BM fungus may act as an allergen, reacting continually in both the upper and lower respiratory tract. The antifungal drug (itraconazole 50 mg/ day) seemed to achieve a partial response. Basidiomycetous fungi may attract attention because of the possibility as a causative antigen in this new clinical concept of SAM. © 2011 The Japanese Society of Internal Medicine.

Summary Background Recently we have reported 5 cases of allergic fungal cough (AFC), which is intractable and is characterized by sensitization to one of basidiomycetous fungus. Because AFC shows good clinical response to antifungal drugs, diagnosing AFC in patients with CIC may lead to the consequent management of CIC. Therefore, we determined the incidence of CIC among our hospital patients, and the frequency of BM fungi in sputum samples collected from patients with CIC. Furthermore we evaluated whether or not a recognizable clinical pattern that distinguishes CIC from non-CIC exists. Methods The medical records of 70 patients complaining of chronic cough who were referred to our hospital for diagnosis and treatment were analyzed retrospectively. Results The primary diagnoses were CIC (27.0%), cough-variant asthma (30.0%), atopic cough (24.3%), sinobronchial syndrome (8.6%), cough-predominant asthma (7.1%), gastro-esophageal reflux (1.4%), and others (1.4%). In CIC patients, the median age, proportion of females, and frequency of acute upper respiratory tract infection did not differ significantly from those in non-CIC patients. CIC patients had a longer median duration of cough (11.0 months vs. 3.5 months). The positive ratio of BM cultured from the sputa of CIC patients (62.5%) was significantly ( p =0.0061) higher than that of non-CIC patients (16.7%). Conclusion The existence of BM fungi in induced sputum may be an important factor for distinguishing the clinical manifestation of CIC from that of non-CIC. The clinical approach from the aspect of fungal allergy may serve as a clue that may aid in the successful management of CIC.

This controlled study was performed to clarify the therapeutic benefit of itraconazole for the treatment of patients with chronic cough, wherein a sputum culture yielded basidiomycetous (BM) fungi.Of the 171 patients who visited our hospital for the diagnosis and treatment of chronic cough, BM was detected in the sputum of 39 patients. Informed consents were obtained from 21 patients who were subsequently enrolled in this trial. After the administration of the standard therapy, all the patients were enrolled in a randomized placebo-controlled study with 2 weeks of treatment with a low dose of itraconazole (50 mg/day) (n = 10) in comparison with a corresponding period of treatment with matched placebo (ambroxol hydrochloride 45 mg/day) (n = 11). Coughing was assessed using subjective cough symptom scale and capsaicin cough challenging.The treatment with itraconazole, but not placebo (p = 0.17), was associated with a significant improvement in the cough scale (p = 0.0051); moreover, the improvement achieved with itraconazole was significant (p0.001) when compared with that of the placebo.Low-dose itraconazole was shown to be an effective antitussive in patients with chronic cough in which sputum examination yielded BM fungi. The 21 patients described here entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. These clinical features may constitute a unique disease concept called fungus-associated chronic cough (FACC).

Total knee arthroplasty (TKA) was carried out on both knee joints for spontaneous bony ankylosis due to rheumatoid arthritis (RA). Preoperative fixation angles were 40 degrees . First, the peroneal nerve was released prior to TKA. Quadriceps snip was performed to evert the patella laterally. Bilateral TKAs were carried out using a stabilized prosthesis. The results showed full extension to 70 degrees flexion at 3 years after the surgery. Absence of pain, maintenance of stability, and walking ability were achieved, without any significant complication. Total knee arthroplasty following takedown of a spontaneous ankylosed knee is an effective procedure under appropriate knee conditions.

Cough variant asthma is recognized to be a precursor of asthma or preasthmatic state because nearly 30% patients with cough variant asthma develop typical asthma within several years. However, predictors for risk of typical asthma onset from cough variant asthma are unknown. Forty-one patients with cough variant asthma (median age 50 years, 13 men and 28 women), who had undertaken spirometry, bronchial reversibility test, methacholine provocation test, measurements of peripheral blood eosinophil count, serum total IgE, and specific IgE to common allergens, and induced sputum eosinophil count at presentation, were followed up with special emphasis on typical asthma onset during 1 year or more (median 4 years, range 1-12.4). Long-term inhaled corticosteroids (ICS) were taken in 27 patients. Univariate and multivariate logistic analyses were performed to determine the predictors for typical asthma onset. Asthma onset was recognized in 7 patients. Bronchial hyperresponsiveness, peripheral blood eosinophil count, and no use of ICS were significant predictors for the typical asthma onset by univariate analysis. However, only bronchial hyperresponsiveness was the significant predictor when multivariate analysis was used (adjusted OR 0.028, 95% CI 0.001-0.783, p = 0.0355). Bronchial hyperresponsiveness may be the most important predictor for risk of typical asthma onset from cough variant asthma.