Bronchial asthma and chronic obstructive pulmonary disease (COPD) are increasing common diseases. The major pathogenesis of both illnesses is chronic inflammation. However, the inflammatory pattern is distinct in each disease. In asthmatic airways, activated mast cells/eosinophils and T helper 2 lymphocytes (Th2) are predominant. In contrast, macrophages and neutrophils are important in COPD airways/lung. Although nitric oxide (NO) hyperproduction due to inducible NO synthase (iNOS) is observed in asthma and COPD, nitrotyrosine formation via the reaction between NO and O₂^- in addition to the myeloperoxidase-mediated pathway. These distinct inflammatory patterns in both diseases seem to cause pathological differences in asthma and COPD.

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Asthma and COPD are complex diseases with strong genetic and environmental components. These common pulmonary diseases have both different and similar clinical features. Molecular genetic techniques are being used to improve understanding of these common late onset disorders. Recently, several genes and genetic loci associated with increased susceptibility to asthma and COPD have been described. Many of these genes are expressed in the lung tissues, indicating that events in lung tissues might drive disease processes. Lung tissues are rich sources of innate danger signals, and an increased understanding of how the lung tissues communicate with the immune system to maintain healthy tissue might provide new insights into the pathogenesis of chronic inflammatory lung diseases in which injury and repair are in disequilibrium. Given that the innate immune system is at the interface between the airways and environmental insults, genetic polymorphisms in genes related to the innate immune system are likely to affect susceptibility to both asthma and COPD. In addition, some findings from genetic studies provide molecular support for the point of view proposed in the Dutch hypothesis regarding the relationship between asthma and COPD, which highlights the complexity of the pathways that can induce small airway disease and suggests that there is a continuum between asthma and COPD.

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Asthma and chronic obstructive pulmonary disease (COPD) are among the most prevalent lung diseases. In both asthma and COPD, airway inflammation leads to airway remodeling. Parenchyma of the lung is also influenced by disease conditions. Airway wall thickening/lumen narrowing and parenchymal destruction occur in COPD. In asthma, airway remodeling contributes to the lung parenchyma. Computed tomography (CT) has been widely used as an imaging tool for lung diseases. With the technical advancement of CT, together with the development of analysis software, it is now possible to analyze the lung parenchymal change and airway remodeling quantitatively using CT. This article reviews the role of CT in assessing the lung structure and functions of patients with asthma and COPD.

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Physiological differences and similarities in asthma and COPD are documented based on respiratory function testing. (1) The airflow reversibility is usually important for the diagnosis of asthma. However, patients with long disease histories may have poor reversibility. The reversibility test in COPD is useful for predicting the treatment response. (2) In some of the stable asthmatic patients without attack, the concave downslope of flow-volume curve is present. In severe COPD, the flow in the second half of the curve is smaller than that of rest-breathing. (3) Inspiratory capacity (IC) is a good estimator of air trapping and of predicting the exercise capacity in COPD or persistent asthma. (4) Peak expiratory flow (PEF) can be an important aid in both diagnosis and monitoring of asthma. PEF is not used in COPD because the main disorder is in the peripheral airway. (5) Measurements of airway responsiveness may help to a diagnosis of asthma. However, many COPD cases also have it. (6) Impulse oscillation system (IOS) revealed that the predominant airway disorders in asthma and COPD are central and peripheral respiratory resistance, respectively. However, some asthma patients have larger values of peripheral component. (7) D_LCO reflects the extent of pathological emphysema and it is useful for the follow-up of COPD, whereas D_LCO is not decreased in asthma. (8) The patient with widened A-aDO₂ and alveolar hypoventilation may lead to the life threatening hypoxia in severe asthma attack or severe COPD. When PaCO₂ overcomes PaO₂, the patient should immediately be treated by mechanical ventilation.

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Many lines of previous studies have reported that differences and similarities between bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). The pathological and physiological abnormalities of these diseases have been also discussed. BA and COPD have some similarities such as airflow obstruction, pulmonary inflammation, and airway hyperresponsiveness (AHR). However, both two diseases are regarded different diseases since their mechanisms of development are quite different. Therefore, both two diseases require different assessment, monitoring, and pharmacological treatments. In this paper, we describe the pharmacological treatment of asthma in adults and COPD based on recently updated guideline by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD), respectively.

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Background: Natural rubber latex (NRL) allergy is a common occupational disease in health care workers (HCW). However, few reports have compared the major allergen of HCWs to those in gloves that are routinely used in the hospital. The aim of this study was to evaluate the major NRL allergens in gloves used by HCWs.
Methods: We studied 20 HCWs who were suspected to have latex allergy (LA). We performed a skin prick test (SPT) using NRL allergens. Serological testing was performed using the ImmunoCAP^TM. The total amount of protein and the antigenic protein concentrations extracted from NRL gloves were measured. Four different types of FITkit^TM were used to measure the concentrations of Hev b 1, 3, 5, and 6.02 in the gloves.
Results: A SPT using NRL extract identified 14 cases with positive reactions. The sensitivity and specificity of the SPT scores to the NRL glove extract were 100%. The sensitivity of latex specific IgE was 100% but the specificity was 14.2%. The sensitivity and specificity of rHev b 6.02 specific IgE were 100% in the LA group. The total amounts of protein from the medical gloves for surgery and examination were 265μg/g and 95μg/g, respectively. The antigenic protein concentrations in the gloves were 24.9μg/g and 1.0μg/g, respectively. The total amounts of the specific four allergens in the NRL gloves were 2.18μg/g and 0.45μg/g, respectively.
Conclusions: We concluded that the main allergen of HCWs who have been sensitized occupationally by NRL gloves was Hev b 6.02.

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Background: Salmeterol and fluticasone propionate combination (SFC) provides better asthma control than fluticasone propionate (FP) alone, however, little is known on the effects of differential treatments on airway function and inflammation in patients with mild asthma.
Methods: We randomized 27 mild persistent asthma patients treated with the equivalent of 400μg beclomethasone dipropionate to receive SFC (50/100μg, 13 patients) or FP (100μg, 14 patients) twice daily for 8 weeks. We compared the effects of SFC and FP on pulmonary function assessed by spirometry and impulse oscillometry (IOS), eosinophil percentage of induced sputum and serum, and with asthma symptoms and control after each treatment.
Results: We observed that SFC significantly improved forced expiratory volume in one second (p < 0.05), IOS measurements of total resistance R5 (p < 0.01), central resistance R20 (p < 0.05), and distal reactance X5 (p < 0.01) compared with FP. The percentage of eosinophils in sputum, but not in serum, decreased significantly more in the SFC group than in the FP group (p < 0.05). There was also a significant improvement in symptom control in the SFC group (p < 0.05).
Conclusions: These findings suggest that SFC is more useful than FP in mild asthma cases. The clinical benefit of SFC provides evidence that IOS and induced sputum allows for the detection of changes in airway function and inflammation.

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Background: Inhaled corticosteroid (ICS) has played an important role in the management of asthma. Although several kinds of ICSs are currently available, there is no established strategy for ICS selection.
Methods: Using the data from the 2004 questionnaire surveys by the Niigata Asthma Treatment Study Group, we analyzed relationships between each patient and the ICS employed on the basis of patient background, asthma control and treatment, and indicated characteristics of ICS selection by the physician.
Results: Of 2852 cases, 2279 (79.9%) were ICS users, and 1513 (66.4% of ICS users) were classified as being in the fluticasone propionate (FP) group, 438 (19.2%) in the budesonide (BUD) group, and 240 (10.5%) in the hydrofluoroalkane-beclometasone (HFA-BDP) group, indicating that FP was a standard ICS in this study. The mean age was significantly lower in the BUD group (52.3+/-18.2 years) and was significantly higher in the HFA-BDP group (59.9+/-17.0 years) than that in the FP group (55.8+/-16.6 yaers). The proportion of female patients was significantly higher not in the HFA-BDP (46.5%) but in the BUD group (59.0%) than in the FP group (51.1%). These results indicated that BUD was frequently prescribed to young female and HFA-BDP was employed in the elderly patients irrespective of gender compared with FP.
Conclusions: Our study indicates that ICS selection is reasonably adapted to each patient's background at least in the surveyed area. We need to elucidate the characteristics of ICS selection further in the future as new ICS and devices are developed.

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Background: Flavonoids are nutrients that exert anti-allergic effects. We investigated the preventative effect of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve the symptoms of Japanese cedar pollinosis.
Methods: In a parallel-group, double-blind placebo-controlled study design, 24 subjects with Japanese cedar pollinosis took 100mg EMIQ or a placebo for 8 weeks, starting 4 weeks prior to the onset of pollen release. Subjective symptoms, ADL scores and the usage of drugs were recorded daily, and the QOL score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum levels of IgE and flavonoids.
Results: During the entire study period, ocular symptom + medication score for the EMIQ group was significantly lower (p < 0.05) than that of the placebo group. When limited to the period, ocular symptom scores (p < 0.05, weeks 5-6), and ocular congestion scores (p < 0.05, weeks 5-6) for the EMIQ group was significantly lower than that for the placebo group while other scores for the EMIQ group, such as ocular itching scores (p = 0.09, weeks 4-5), lacrimation scores (p = 0.07, weeks 5-6), and ocular congestion scores (p = 0.06, weeks 4-5), all tended to be lower. However no significant differences were found in nasal symptoms between the two groups. Serum concentrations of IgE were not significantly downregulated but the serum concentrations of quercetin and its derivatives were elevated significantly by the intake of EMIQ.
Conclusions: Intake of the quercetin glycoside EMIQ proved to be effective for the relief of ocular symptoms caused by Japanese cedar pollinosis.

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Background: The most common type of pollinosis in Japan is Japanese cedar pollinosis (JCP). While forest walking is a common form of recreation for Japanese people, it has been unclear whether forest walkers with JCP still choose to visit forested areas during the pollen season or whether they avoid those areas, and as such, the aim of this study was to investigate this question.
Methods: The study participants were all healthy men and women volunteers aged 20 years or over who visited the Tokyo University Forest in Chiba during 4 different days. The survey was conducted using self-administered questionnaires.
Results: The number of available responses was 498. Of these, 112 participants who experienced JCP were included in the analysis. Seventy-three participants (65.2%) responded that they visit forests even during the pollen season. The association between forest walking choices during the pollen season and self-rated levels of pollinosis symptoms was not statistically significant (Cramer's V = 0.13, p = 0.47). As many as 60% of the participants who reported serious symptom levels responded that they visit forested areas even during the pollen season.
Conclusions: These results revealed that two thirds of forest walkers who had experienced JCP visited forests even during the pollen season. This indicates the further need for public service announcements informing people with JCP that the risk of pollen exposure and subsequent JCP reaction is increased by visiting forested areas during the pollen season.

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Background: Immunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established. In this study we investigated the role of ST in leukotriene receptor antagonist (LTRA) non-responders with mild-to-moderate persistent asthma before initiating corticosteroids inhalation therapy.
Methods: This was a prospective open-level clinical trial. LTRAs was given to 41 patients with asthma for 4 weeks and clinical efficacy was assessed using daily symptom scores. The 10 patients, aged 2.5-8.5 years, who failed to show clinical improvement, were defined as LTRA non-responders. After a 1-week washout period, the efficacy of ST was investigated and compared with LTRA non-responders for the following 4 weeks.
Results: LTRA non-responders showed a significant improvement in the average symptom score, peak expiratory flow, use of rescue medication and the proportion of symptom-free days with ST therapy.
Conclusions: ST is a good choice for patients who have failed to respond to LTRAs. ST should therefore be added to the list of treatment options for such patients.

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Background: Gastroesophageal reflux disease (GERD) is diagnosed by the reflux index of 24-hour pH monitoring (pH monitoring). In our previous study, GER episodes during the upright position were more frequent than those during the supine position in asthmatic children. In this study, we investigated the clinical usefulness of the mean hourly number of acid refluxes, designated as the mean number of acid refluxes/hour (h) during the upright position in addition to the pH index for the diagnosis of GERD.
Methods: The subjects were 22 preschool asthmatic children. When the reflux index was over 4% or the mean number of acid refluxes/h during the upright position were three times more frequent than those during the supine position even if the reflux index was below 4%, we prescribed famotidine. Children whose asthmatic symptoms improved with famotidine were included in a GERD group. Children who did not meet the criteria by pH monitoring were included in a non-GERD group in asthmatic children.
Results: The GERD group was comprised of 9 children. In 2 out of 9 GERD group children, the reflux index was below 4%. The median of the mean number of acid refluxes/h during the upright position was 12.9 in the GERD group, and 3.15 in the non-GERD group. The mean number of acid refluxes/h during the upright position were associated with asthmatic symptoms (p < 0.05).
Conclusions: Reflux during the upright position was associated with asthmatic symptoms. The mean number of acid refluxes/h during the upright position in addition to the reflux index could be useful in the diagnosis of GERD when associated with asthma.

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Background: Goblet cell hyperplasia with mucus hypersecretion contribute to increased morbidity and mortality in bronchial asthma. We have reported that thioredoxin 1 (TRX1), a redox (reduction/oxidation)-active protein acting as a strong antioxidant, inhibits pulmonary eosinophilic inflammation and production of chemokines and Th2 cytokines in the lungs, thus decreasing airway hyperresponsiveness (AHR) and airway remodeling in mouse asthma models. In the present study, we investigated whether endogenous or exogenous TRX1 inhibits goblet cell hyperplasia in a mouse asthma model involving chronic exposure to antigen.
Methods: We used wild-type Balb/c mice and Balb/c background human TRX1-transgenic mice constitutively overproducing human TRX1 protein in the lungs. Mice were sensitized 7 times (days 0 to 12) and then challenged 9 times with ovalbumin (OVA) (days 19 to 45). Every second day from days 18 to 44 (14 times) or days 35 to 45 (6 times), Balb/c mice were treated with 40μg recombinant human TRX1 (rhTRX1) protein. Goblet cells in the lungs were examined quantitatively on day 34 or 45.
Results: Goblet cell hyperplasia was significantly prevented in TRX1-transgenic mice in comparison with TRX1 transgene-negative mice. rhTRX1 administration during OVA challenge (days 18 to 44) significantly inhibited goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice. Moreover, rhTRX1 administration after the establishment of goblet cell hyperplasia (days 35 to 45) also significantly ameliorated goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice.
Conclusions: Our results suggest that TRX1 prevents the development of goblet cell hyperplasia, and also ameliorates established goblet cell hyperplasia.

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Background: Ag-dependent activation of IgE-bearing mast cells is a critical first step in immediate hypersensitivity and other allergic responses. Recent studies have revealed Ag-independent effects of monoclonal mouse IgE molecules on mast cell survival and activation. However, no studies have been performed on the effects of polyclonal IgE molecules. Here, we tested whether polyclonal mouse and human IgE molecules affect survival and cytokine production in mast cells.
Methods: Mast cells were cultured in the presence of polyclonal mouse and human IgE molecules, and cell survival and cytokine production were analyzed.
Results: Polyclonal mouse IgE molecules in sera from mice with atopic dermatitis-like allergic skin inflammation, enhanced survival and cytokine production in mast cell cultures. Similar to the effects of monoclonal IgE, the polyclonal IgE effects were mediated by the high-affinity IgE receptor, FcεRI. Human polyclonal IgE molecules present in sera from atopic dermatitis patients were also capable of activating mast cells, and inducing IL-8 production in human cord blood-derived mast cells.
Conclusions: These results imply that polyclonal IgE in atopic dermatitis and other atopic conditions might modulate mast cell number and function, thus amplifying the allergic response.

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Background: Although many patients who experience chest pain or pressure consult their physicians, unfortunately a large number of them do not, and consequently they remain undiagnosed and untreated. Chest pain, in a subset of these patients, may be relieved with a bronchodilator or other asthma drugs.
Methods: This retrospective study included twenty cases of chest pain that were relieved with asthma drugs. Chest pain was categorized into three types: chest pain variant asthma, bronchial asthma with chest pain, and non-asthmatic allergic chest pain. Chest pain variant asthma was defined as chest pressure that improved in response to a bronchodilator, without the characteristic attacks of bronchial asthma. Bronchial asthma with chest pain was defined as chest pressure, with the characteristic attacks of bronchial asthma that improved following the administration of a leukotriene receptor antagonist, systemic corticosteroid, or bronchodilator. Non-asthmatic allergic chest pain was defined as chest pressure without the typical asthma attack, but with chest pressure that improved in response to a leukotriene receptor antagonist or systemic corticosteroid, but not a bronchodilator.
Results: Fourteen cases of chest pain were diagnosed as variant asthma, three cases were diagnosed as bronchial asthma with chest pain, and three cases were diagnosed as non-asthmatic allergic chest pain.
Conclusions: The results suggest that the mechanism underlying chest pain that is relieved with asthma drugs can involve either an airway constriction pathway or a non-constrictive pathway presumably airway inflammation. Analysis of the patient's response to treatment with asthma medication is useful for the correct diagnosis of the source of chest pain.

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Background: Profilin is a panallergen that is recognized by IgE in allergic patients. Allergy to saffron (Crocus sativus) pollen has been described in people exposed to its pollen. Saffron contains a profilin that may cause allergic reactions in atopic subjects. The aim of this study was to describe the cloning, expression and purification of saffron profilin from pollen.
Methods: Cloning of saffron profilin was performed by polymerase chain reaction using specific primers from saffron pollen RNA. Expression was carried out in Escherichia coli BL21 (DE3) using a vector pET-102- TOPO. A recombinant fusion protein was expressed and the recombinant profilin was purified by metal precipitation. Immunological characterization was performed by immunoblotting experiments.
Results: The 34kDa- recombinant saffron profilin, Cro s 2, as a fusion protein was purified. Immunoblotting tested with the sera of allergic patients showed a specific reaction with the recombinant Cro s 2 band.
Conclusions: The sequence of Cro s 2 showed a high degree of identity and similarity to other plant profilins and the recombinant saffron profilin, Cro s 2, may be used for target-specific diagnosis and structural analyses and investigation of cross reactivity of Cro s 2 with other plant profilins.

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Background: We previously reported that 'benifuuki' green tea containing O-methylated catechin significantly relieved the symptoms of perennial or seasonal rhinitis compared with a placebo green tea that did not contain O-methylated catechin in randomized double-blind clinical trials. In this study we assessed the effects of 'benifuuki' green tea on clinical symptoms of seasonal allergic rhinitis.
Methods: An open-label, single-dose, randomized, parallel-group study was performed on 38 subjects with Japanese cedar pollinosis. The subjects were randomly assigned to long-term (December 27, 2006 - April 8, 2007, 1.5 months before pollen exposure) or short-term (February 15, 2007: after cedar pollen dispersal - April 8, 2007) drinking of a 'benifuuki' tea drink containing 34mg O-methylated catechin per day. Each subject recorded their daily symptom scores in a diary. The primary efficacy variable was the mean weekly nasal symptom medication score during the study period.
Results: The nasal symptom medication score in the long-term intake group was significantly lower than that of the short-term intake group at the peak of pollen dispersal. The symptom scores for throat pain, nose-blowing, tears, and hindrance to activities of daily living were significantly better in the long-term group than the short-term group. In particular, the differences in the symptom scores for throat pain and nose-blowing between the 2 groups were marked.
Conclusions: We conclude that drinking 'benifuuki' tea for 1.5 months prior to the cedar pollen season is effective in reducing symptom scores for Japanese cedar pollinosis.

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Background: Influenza A viral infection is concerned with induction of asthma. CD11c⁺ pulmonary antigen presenting cells (APCs) play a central role in sensitization with inhaled antigens during the acute phase of influenza A viral infection and also reside on bronchial epithelium for the long term after sensitization. To investigate the role of CD11c⁺ pulmonary APCs in the inhaled antigen sensitization during the acute phase of influenza A viral infection, we analyzed their function.
Methods: Mice were infected with influenza A virus and were sensitized intranasally with BSA/alum during the acute phase of influenza A viral infection. Expression of surface antigens on CD11c⁺ pulmonary APCs was analyzed by FACS. Cytokine production from CD11c⁺ pulmonary APCs, and interaction between CD11c⁺ pulmonary APCs and naïve CD4⁺ T cells was assessed by ELISA. Ability of antigen presentation by CD11c⁺ pulmonary APCs was measured by proliferation assay.
Results: BSA antigen sensitization during the acute phase of influenza A viral infection induced eosinophil recruitment into the lungs after BSA antigen challenge and moderately increased expression of MHC class II molecules on CD11c⁺ pulmonary APCs. The interaction between the CD11c⁺ pulmonary APCs and naïve CD4⁺ T cells secreted large amounts of IL-10.
Conclusions: BSA antigen sensitization during the acute phase of influenza A viral infection enhanced IL-10 production from naïve CD4⁺ T cell interaction with CD11c⁺ pulmonary APCs. The IL-10 secretion evoked Th2 responses in the lungs with downregulation of Th1 responses and was important for the eosinophil recruitment into the lungs after BSA antigen challenge.

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