Clinical & Experimental Allergy Reviews最新文献

Many changes to our medical care services are expected to occur in the next several years, and these will substantially affect the treatment of pollinosis. Patients with pollinosis are becoming increasingly dependent on over-the-counter (OTC) medicines; today, as many as 25–30% of patients with allergic rhinitis report using these agents. This trend will be further accelerated if switched OTC medicines such as ketotifen and azelastine are sold at general retailers as well as pharmacies and drug stores under new laws. We conducted three surveys on the prescription pattern of drugs against pollinosis during the high pollen count season in 1998, 2003, and 2009. Whereas the use of chemical mediator-release inhibitors tended to decrease, that of second-generation antihistamines increased during the period examined. Especially, use of anti-leukotrienes and prostaglandin D₂/chemoattractant receptor-homologous molecule expressed on Th2 cells antagonists either alone or in combination increased rapidly after their launch in 2000. Despite many successful advances in treatment, however, many patients still remain dissatisfied with their anti-pollinosis therapy. Therefore, it is essential that physicians keep abreast of what medications are to be switched to OTC status and to maintain patient satisfaction by the appropriate use of good prescription drugs.

A nationwide epidemiologic survey of atopic diseases including allergic pollinosis was conducted in 9656 Japanese otorhinolaryngologists and their family members during the Japanese cedar pollen dispersion season in 2008 using methods identical to a previous survey that was performed in 1998. The survey response rate was 37.7% (compared with 42.8% in 1998). The overall prevalence rate of Japanese cedar pollinosis was 26.5%, which is an increase of approximately 9% from that noted in 1998. Similar increases were observed in all age groups, and the prevalence rate was similar between male and female respondents. A unimodal distribution was observed in male and female subjects, with a peak in both men and women aged in their 40s. Nationwide, a consistent positive relation was observed between the prevalence of Japanese cedar pollinosis and the regional Japanese cedar pollen counts. The prevalence rate of pollinosis other than Japanese cedar pollinosis and of perennial allergic rhinitis was 15.4% and 23.3%, respectively; both disease entities tended to occur more frequently in male than in female subjects. The prevalence rate of asthma, atopic dermatitis, and food allergy was 5.2%, 14.1%, and 3.9%, respectively. Our results suggest that the prevalence rates of atopic diseases including Japanese cedar pollinosis are dramatically increasing across all age groups in Japan. In particular, the increasing prevalence rate of Japanese cedar pollinosis seems to reflect higher exposure to the Japanese cedar pollen antigen in many prefectures.

There are similarities between allergic rhinitis (AR) and atopic bronchial asthma in their pathophysiology, although some differences also exist. For example, some AR patients without asthma demonstrate airway hyperresponsiveness (AHR) of the lower respiratory tract. Similar findings have been noted in patients with atopic dermatitis. This indicates that a systemic sensitization to antigen itself plays a pivotal role in the induction of AHR in sensitized individuals independently of eosinophilic inflammation in the lower airway. To clarify the mechanism, we studied a mouse model and found that transfer of antigen-induced memory/effector cells can induce AHR in normal mice without airway inflammation. Dendritic cells (DCs) play a critical role in antigen-induced immune response. We investigated the role of cysteinyl leukotrienes (cysLTs) in DC functions. BALB/c mice were sensitized with ovalbumin (OVA) and aluminium hydroxide (alum) twice, and subjected to OVA inhalation to induce airway inflammation. Systemic OVA sensitization alone up-regulated cysLTs in the lung and stimulated T-helper type 2 (Th2) cytokines production, whereas leukotriene receptor antagonist (LTRA) suppressed these productions. OVA sensitization enhanced DC functions such as antigen-presenting capacity and cytokine production, and LTRA also attenuated them. Finally, we treated mice with LTRA during systemic sensitization and examined the effect on subsequent airway inflammation induced by OVA inhalation. LTRA suppressed all indicators of inflammation such as airway eosinophilia, Th2-type cytokine production, and AHR along with decreased DC functions of the lung. These results indicate that modulating the antigen-induced up-regulation of DC functions in the early phase could attenuate further development of eosinophilic inflammation in the lower airway. Taking the similarities of lower and nasal airway into account, cysLTs may also play a critical role in the pathogenesis of AR; therefore, LTRA could be effective against AR from the initial presentation to the inflammation phase.

The original initial therapy against pollinosis was introduced to the clinical setting in Japan in the 1980s, led by the launch of anti-allergic drugs that were expected to exert prophylactic effects. The purpose of the therapy was to control the typical pollinosis seen in Japan: that occurs due to Japanese cedar/Japanese cypress pollens. The original therapy included prophylactic use of anti-allergic drugs administered from before the start of the pollen season. Thanks to the launch of epinastine hydrochloride – which allows long-term use, exerts adequate effects by once-daily dosing, and seldom causes drowsiness as an adverse reaction – the initial therapy became safer and more defined. Meanwhile, precision of pollen-dispersion forecast improved, automatic counting of dispersed pollen grains became available, and real-time access to pollen-dispersion information was facilitated due to widespread Internet use. Today, the initial therapy has improved to be a scheduled, comprehensive regimen that adopts hyposensitization as a fundamental procedure and incorporates measures against aggravation factors before the pollen season and complications likely to occur after the pollen season. Every day, we are practising this therapy and achieving great results; we believe that this regimen will benefit many people who suffer from pollinosis.

Nasal obstruction is a crucial symptom in allergic rhinitis (AR) patients and may affect the quality of life. It is caused mostly by nasal mucosal obstruction, and to a lesser extent, fluid secretion. Mucosal congestion is primarily a vascular phenomenon comprising vasodilatation of capacitance vessels (cavernous sinus) and oedema formation due to plasma leakage from post-capillary venules. The nose has a complex microvascular anatomy consisting of capacitance vessels, arteriovenous anastomosis, and subepithelial and periglandular capillaries. Nasal congestion is explained by the effects of local mediators exerting potent vasodilatation or increasing permeability of nasal blood vessels and nerves. Capacitance vessels usually constrict because of constant sympathetic tone. They distend by a variety of stimuli such as loss of continuous sympathetic stimulation on the sinusoids, direct vasodilatation by vasoactive substances, contraction of cushion veins, and compression of venules by distended arteries in the intraosseous bony canals of periosteal space. Although topical application of histamine can cause vasodilatation and oedema, histamine is not likely a major mediator causative of nasal congestion in AR. Nasal vascular dilatation elicited by cysleukotriene 1 (cysLT₁) may be induced by nitric oxide produced through cysLT₁ receptor activation. Thromboxane A₂ may cause capacitance vessel dilatation through a contraction of cushion veins. Potentiation of vasoconstrictor action of steroids has been reported since the 1950s. Glucocorticoids (GCs) have two fundamentally different vascular effects: classic action modifying the transcription of pro-inflammatory genes and acute non-genomic action (within minutes) that increases the vasomotor tone. The non-genomic effect is likely related to binding of GCs to the plasma membrane and inhibition of extraneuronal monoamine transporter on vascular smooth muscle cells, thereby increasing noradrenaline concentrations at α₁-adrenoceptors. Genomic vascular effects include the reduction of vessel density, decrease of hyperperfusion, reduction of inflammatory microvascular hyperpermeability, and decreased influx and activation of inflammatory cells. These effects require hours to manifest themselves physiologically.

In 2006, a survey was conducted to estimate the prevalence of Japanese cedar pollinosis in three target areas in Tokyo, namely Akiruno-shi, Chofu-shi, and Ota-ku; this survey was similar to two surveys conducted previously, in 1983–1987 (first survey) and 1996 (second survey). In the most recent survey, the overall prevalence of Japanese cedar pollinosis in Tokyo, except the islands of Tokyo, was estimated as 28.2%. This prevalence rate exceeds that estimated by the first and second surveys by 18.2 and 8.8 percentage points, respectively. The prevalence of Japanese cedar pollinosis in the three survey target areas increased by 2.3–10.8 percentage points vs. the rates obtained in the second survey. Furthermore, differences among the prevalence rates in the three areas decreased. Compared with the results obtained in the second survey, increases in the prevalence rate were noted in all age groups other than in people aged 30–44 years. In particular, the prevalence rate in children aged 0–14 years increased markedly, showing a threefold increase. The prevalence rate exceeded 30% in all age groups between 15 and 59 years.

The possible cure of Japanese cedar pollen-induced allergic rhinitis (AR) by immunotherapy was investigated. The mechanism of cure was also studied from the viewpoint of the T cell response to allergen; it was documented that absence of IL-5 production from allergen-stimulated T cells was the major mechanism. The prophylactic aspect of immunotherapy was also investigated. Eighty-eight asymptomatic subjects who were already sensitized to pollen were recruited. Of these subjects, 31 (prophylactic immunotherapy group) were treated with pollen immunotherapy for 3 years. The remaining 57 individuals (control group) were not treated with pollen immunotherapy. At the end of the 3-year trial, only 28 of 57 individuals (49.1%) in the control group remained asymptomatic. On the other hand, 27 of 31 individuals (87.1%) in the prophylactic immunotherapy group remained asymptomatic. Prophylactic immunotherapy decreased IL-4 synthesis from pollen allergen-stimulated T cells, suggesting that this was the mechanism of prevention of symptoms' outbreak. We next examined whether mite immunotherapy for patients monosensitized to mite allergen could prevent new sensitization to pollens. A total of 132 patients monosensitized to house dust mites were included. Of these individuals, 52 (pharmacotherapy group) were treated with antihistamine tablets for 4 years, and the remaining 80 patients (mite immunotherapy group) were treated with mite immunotherapy for the same time period. Whereas 15 of 52 patients (28.8%) in the pharmacotherapy group attained new sensitization to some kinds of pollen allergens, only five of 80 patients (6.3%) in the mite immunotherapy group attained new sensitization. Our data suggest that mite immunotherapy can prevent new sensitization to pollen allergens. It is therefore concluded that pollen immunotherapy cannot only cure pollen-induced AR but also prevent outbreaks of pollen-induced AR, and that mite immunotherapy can prevent new sensitization to pollen allergens.

We believe that this century will be the century of quality of life (QOL). Both medical prediction and QOL prediction are indispensable in clinical practice. Therefore, we investigated how to predict QOL outcomes after various therapeutic interventions using our customized questionnaire. Seventy-four cataractus patients treated with day surgery (S1), 106 undergoing renal transplantation (S2), 30 with pacemaker treatment (S3), and 36 elderly persons supported by government-mandatory nursing/healthcare service for persons aged >65 years (S4) participated in this study. Our self-administered questionnaires and the Life Satisfaction Index (LSI) were at first compared. Pearson's correlation coefficients between our questionnaires and LSI were S1, r=0.92 (P<0.05); S2, r=0.69 (P<0.01); and S3, r=0.87 (P<0.01). Cronbach's α coefficients of our questionnaires were high enough for acceptance for clinical use. Our questionnaires contained 11 (S1), 11 (S2), 9 (S3), and 12 (S4) main factors and the cumulative contributions were 0.82, 0.77, 0.85, and 0.81, respectively. Whereas all patients whose baseline QOL was low before interventions exhibited improved total QOL after interventions, most patients whose total QOL was high before interventions underwent impaired total QOL thereafter. Divergent points were identified for QOL improvement or deterioration after therapeutic interventions according to each disorder investigated. Significant negative correlations were noted between baseline QOL and QOL changes. Our QOL prediction theory may be helpful when discussing interventions with individual patients in a range of therapeutic settings.

Many different surgical procedures have been described to alleviate nasal obstruction due to turbinate hypertrophy in patients with allergic rhinitis (AR) who continuously have chronic nasal congestion. The goal of surgical procedures should be ‘optimal reduction of volume and secretion with preservation of function’. For a period of about 25 years, laser surgery of the inferior turbinate has been considered a simple and effective surgical treatment with a low complication rate that has been in widespread use by many ENT surgeons. Various trials have demonstrated the clinical effectiveness of a series of different laser systems including carbon dioxide, Nd:YAG, potassium-titanyl-phosphate, and diode laser. Laser surgery generally induces significant increases of the total volume of the nasal cavity. Several studies have provided evidence that the expression degree of local inflammatory cytokines and chemical mediators can be attenuated by the treatment. The mucociliary function of the inferior turbinate seems to be preserved after CO₂ laser intervention. A breakthrough in the surgical procedures available for allergic patients who severely suffer from both intractable hypertrophic inferior turbinates and unregulated nasal secretion was introduced in Japan. Posterior nasal neurectomy is a novel alternative method in which neural bundles are selectively cut or cauterized from the sphenopalatine foramen. Resection of the posterior nasal nerve at this point enables surgeons to inhibit the parasympathetic nerve function of the nasal mucosa with no troublesome complications such as decrease of lacrimal secretion. The procedure simultaneously provides interruption of the somatic afferent innervation to the turbinate mucosa. Herein we assess the clinical effectiveness of this surgical procedure based on objective and measurable monitoring parameters and discuss the underlying therapeutic mechanisms.