Asthma is defined as a lung disease characterized by airway obstruction and/or narrowing. This condition is usually reversible, either spontaneously or with treatment. In addition, an important feature of the disease is airway inflammation. Attention to this is a major focus of therapy. Somewhat related to the inflammatory condition and somewhat to hereditary and environmental factors is the feature of airways hyper-responsiveness. Much of what is currently taught in the United States today concerning asthma pathophysiology and treatment emanates from guidelines that were issued in 1991 and that are currently being revised. This guideline initiative has been sponsored by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health. As a large and influential government agency, the NHLBI has provided the financial and human resources to distribute important information to patients, their families and doctors. There are several aspects that should be stressed concerning these guidelines. The importance given to the concept of airway inflammation in contrast to the idea of simple bronchospasm being the main feature of asthma has already been highlighted. Related to this is the idea of early intervention with anti-inflammatory therapy rather than use of beta-agonist bronchodilators alone.
It has been difficult to achieve acceptance of this concept by patients and physicians, because chronic use of a medication is foreign to many and is also costly. A great deal of the time of American asthma specialists is devoted to educating their patients on the importance of chronic anti-inflammatory therapy. Another important focus is the environment. The role of the housedust mite, indoor pets, molds and cockroaches in increasing airway inflammation in allergic asthmatic patients is receiving growing attention. Diagnosing the allergic component of the disorder with allergy skin tests or RAST and then acting on the environment to remove major allergens is now considered to be of paramount importance. Another important aspect of care that has been overlooked in the past is the need to monitor pulmonary function with some regularity. This should be done at visits to both the asthma specialist and family doctor. Some patients require daily home monitoring with the use of a peak flow meter. Both patients and physicians have failed to recognize that significant airway obstruction can occur before there are symptoms. Pulmonary function monitoring is the only way that this situation can be tracked and recognized early in the development of an attack.
American physicians are trained to believe that the success of their treatment plan depends on communication with patients and families. They generally recognize the need to simplify the regimen, to provide written information reinforcing their instructions, to repeat these at each visit, and to observe the patient who uses metered dose inhalers. Many communities in the US have support groups for patients and families with asthma, which allow people to come together to share their concerns and frustrations. This seems to enhance compliance with medical therapy, as patients feel they are more involved in their disease than if they were passive recipients of information. Federal programs are ongoing to assess the outcome of these support interventions.

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Recent clinical and experimental animal studies have provided evidence for a pivotal role of T lymphocytes and Th2 cytokines in the development of allergic inflammatory responses and airway hyperreactivity. These studies suggest also that the Th2 cytokine-associated inflammatory responses are potential targets of developing novel and effective therapies. Using a novel gene-transfer approach, we investigated the role of a Th2-inhibitory cytokine, IFN-γ, in the regulation of antigen (Ag)-induced lung inflammatory response and airway hyperreactivity by transfer of the IFN-γ gene into mouse lung mucosal cells. Our results showed that mice receiving the IFN-γ gene demonstrate a lower degree of Ag- and Th2 cell-induced airway hyperresponsiveness and a reduced eosinophilia in the lung. These results provided evidence that the instillation of the IFN-γ gene into the lung is effective in modulating the allergic inflammation and bronchial hyperreactivity in an experimental animal model.

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The field of chronobiology and chronotherapy in medicine is in its relative infancy. However, important knowledge has been gained so as to better understand both the pathophysiology of diseases and the corresponding therapeutic interventions. Asthma is one of the disease entities that has been studied in detail in regard to both time related alterations in pathophysiology and treatment. This article reviews the nocturnal worsening of asthma.

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Steroid inhalation therapy is recommended for treatment of moderate to severe asthma, but it is unknown whether the therapy sufficiently suppresses production of thromboxane A₂ (TXA₂), one of the inflammatory lipid mediators. The effect of a selective orally active thromboxane synthesis inhibitor, ozagrel hydrochloride (200mg twice a day for 4 weeks), on morning and evening peak expiratory flow (PEF) was examined in 70 stable asthmatics receiving beclomethasone diproprionate (BDP) inhalation therapy (800μg/day) by a randomized, placebo-controlled, single-blinded study. Morning PEF was significantly increased from 313.5±13.1 (mean±SEM) L/min to 325.7±12.2L/min at 1 week, 335.5±12.7L/min at 2 weeks, 338.6±13.4L/min at 3 weeks, and 340.0±13.2L/min at 4 weeks in 35 patients treated with ozagrel but not in the other 35 patients treated with a placebo. The percent increase in the morning PEF was significantly greater with ozagrel than with the placebo. It is speculated that inhibition of thromboxane synthesis by medium dose of steroid inhalation therapy may be insufficient in some asthmatics.

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In cases of occupational asthma due to reactive chemicals, an appreciable number of patients have persistent asthmatic symptoms and airway inflammation even after several years' avoidance of the cause agents. A case of late respiratory systemic syndrome (LRSS) caused by phthalic anhydride is reported. The patient showed a progression of bronchial asthma due to house dust mite and developed a new bronchial sensitization to horse hair during the 5 year follow-up period. The patient was diagnosed in September 1990 as having LRSS due to phthalic anhydride. He was atopic and had worked in a factory preparing materials for paints for 8 years. After leaving his workplace and commencing treatment with anti-asthmatic medications, his asthmatic symptoms and airway hyper-responsiveness were much improved for 1 year (PC20 methacholine level was increased from 0.44 to 4.4mg/mL). For several months before the second admission (October 1992) his asthmatic symptoms were again aggravated and methacholine PC20 decreased to 1.1mg/mL without improvement in the following 3 years. The level of serum specific IgE antibody to phthalic anhydride has been gradually decreasing, while specific IgE to two types of house dust mite and horse hair has been increasing year by year during the last 3 years' follow-up period. These findings suggest that chronic exposure to inhalant allergens can induce the progression of allergen-induced airway inflammation, and result in new bronchial sensitization to inhalant allergens. Careful follow-up study is needed to detect new developments of allergen-induced bronchoconstriction in occupational asthma patients with persistent asthmatic symptoms.

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Using a murine model, topical application of glucocorticoid ([GC], 50μg diflucortolone valerate in ethanol) on a sensitized site (flank skin) for 7 times before and 2 times after sensitization on alternate days, augmented expression of contact sensitivity reactions on the challenged site (ear skin). This augmentation was due to the systemic effect of percutaneously absorbed GC, because topical GC also augmented the skin reaction in mice that had been sensitized on a separate site from that of the GC application. In contrast, topical application of GC inhibited the contact sensitivity skin reaction when applied on the challenged sites. Intraperitoneal injection of the same dose of GC also failed to augment the skin reactions. Glucocorticoid augmented the contact sensitivity skin reactions and these persisted for 96h after the control skin reactions subsided. Early phase (1-6h) skin reactions were also induced or augmented when dinitrofluorobenzene or trinitrochlorobenzene but not oxazolone were used as the sensitizer; GC also augmented the non-specific reactions to croton oil or to suboptimal concentration of hapten in normal mice. The numbers of Langerhans cells (LC) were reduced in both the GC-application and challenged sites. Haptenated LC from GC-treated skin showed a rather weak sensitizing ability, which was not statistically significant. Transfer of lymph node cells and/or spleen cells or serum from GC-pre-treated mice failed to induce a contact sensitivity reaction in normal recipient mice. These results suggest that topical GC might augment cutaneous inflammation through a possible modulation of local cytokine production, regardless of the number of LC or the presence of sensitized lymphocytes.

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Twenty-two Japanese chironomid species were examined for their allergenicities using ELISA with the sera of 32 asthmatic patients. The species Paratrichocladius rufiventris and Cricotopus sylvestris showed high positive rates of specific IgE, high average IgE reactivities and high frequencies of strong IgE reactivity and the highest IgE reactivity of the 22 species, suggesting a high rate of contact with humans and the possession of highly allergenic components by these two species. In contrast, Tanypus punctipennis and Rheotanytarsus kyotoensis showed low allergenicities, suggesting a low level of human contact and/or a lack of allergenic components. Furthermore, species that emerge from eutrophic waters in a large mass, such as Macropelopia paranebulosa, Paratrichocladius rufiventris and Chironomus yoshimatsui, showed strong allergenicities in all the tests. This suggests that eutrophic water be regarded as an important reservoir to allergenic chironomids.

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Gastroesophageal reflux (GER) has been reported as a cause of chronic cough (CC) in the United States. It has been reported that 5-21% of CC cases are induced by GER. In Japan, however, detailed clinical features of CC induced by GER have not been described. The present study reports on six Japanese patients with GER-induced CC. The subjects were all females, with a mean age of 72 years. The average body mass index was 37kg/m², indicating obesity. No abnormalities were found with regard to concentrations of C-reactive protein, peripheral eosinophil counts, serum IgE concentrations, serum titers of cold agglutinins or antibodies to Mycoplasma pneumoniae, chest radiograph findings, respiratory function tests or blood gas analyses. Bronchial biopsy was performed in three patients and showed chronic inflammation characterized by lymphocytic infiltration, squamous metaplasia and mucosal basement membrane thickening. In the study population (Japanese patients), GER-induced CC tended to occur in elderly obese women and may be attributable to airway inflammation.

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