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Nasal polyps: effects of seasonal allergen exposure.

Nasal polyps are characterized by chronic eosinophilic inflammation and often coexist with rhinitis and asthma. Many patients with polyps have no detectable allergy, and it is considered that allergy, at least in many cases, is not relevant to polyp to pathogenesis. To explore the association of nasal polyps with allergy, 16 patients with polyps and ragweed allergy (PRW +) and 16 patients with polyps who were not allergic to ragweed (PRW-) were compared with patients without polyps, 16 who were allergic to ragweed (NPRW +) and 16 who were not allergic to ragweed (NPRW-), before and during the ragweed season. The level of ragweed allergy was comparable in the PRW+ and NPRW+ populations as determined by ragweed skin test wheal diameter, ragweed IgE RAST percent binding, and total serum IgE. Symptom scores before the ragweed season recorded on visual analog scales for the symptoms of blockage, sneezing, decreased smell, itch, postnatal drip, and runny nose were high in patients in the PRW+ and PRW- groups and did not change during ragweed season. Mean symptom scores were low in the NPRW+ group before ragweed season and increased during the season to levels similar to those of patients in the PRW+ and PRW- groups. Preseason nasal lavage albumin concentration was higher in subjects with polyps than those without polyps (58.5, 98) versus (13.6, 15 micrograms/ml) (p = 0.02) and did not change significantly in any group with seasonal exposure. Data are presented as mean, 1 SD; comparisons are made with unpaired t tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitis.

Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 microg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and alpha2-macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of alpha2-macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in alpha2-macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects.

Administration, Topical↗

Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium.

BACKGROUND: Symptoms of allergic rhinitis are accompanied by infiltration of the nasal mucosa with inflammatory cells, predominantly eosinophils and metachromatic cells (basophils and mast cells). Specific immunotherapy (IT) reduces mucosal eosinophilia and numbers of metachromatic cells in the epithelium. A specific marker distinguishing basophils from mast cells was recently developed. OBJECTIVES: The basophil-specific monoclonal antibody 2D7 was used to determine the influence of subcutaneous IT on numbers of nasal mucosal basophils compared with the effects of IT on neutrophils, eosinophils and mast cells. METHOD: During a randomized, placebo-controlled trial of grass pollen IT in 44 adults with severe summer hay fever, nasal biopsies were taken at baseline, out of the pollen season, and at the peak of the pollen season following 2 years treatment. Biopsies were processed for immunohistochemistry for basophils (2D7+), mast cells (AA1+), eosinophils (MBP+) and neutrophils (neutrophil elastase+). RESULTS: In placebo-treated (PL) patients there were significant seasonal increases in basophils (P < 0.01), mast cells (P < 0.05) and eosinophils (P = 0.002) in the nasal submucosa. In IT-treated patients significant increases in 2D7+ cells (P < 0.01) and eosinophils (P = 0.01) but not AA1+ cells (P = 0.9) were observed. These differences were significant between groups for eosinophils (P < 0.05). In the epithelium there were seasonal increases in AA1+ cells and eosinophils in both groups (PL: P < 0.01, IT: P < 0.05 for both). The between-group difference was significant for eosinophils (P = 0.05). Basophils were observed in the epithelium of six out of 17 in the placebo group and one out of 20 in the IT group (P = 0.03). Neutrophil numbers remained constant in both epithelium and submucosa. CONCLUSION: Successful grass pollen immunotherapy was associated with inhibition of seasonal increases in basophils and eosinophils, but not mast cells or neutrophils within the nasal epithelium. Immunotherapy may act, at least in part, by reducing seasonal recruitment of basophils and eosinophils into the epithelium.

Adult↗

Reduced airway absorption in seasonal allergic rhinitis.

The common notion that increased mucosal absorption characterizes allergic and inflamed airways is poorly supported by physiologic in vivo data. We have now examined whether the airway mucosa of patients with seasonal allergic rhinitis develop a change in absorption during their active disease period. Twelve patients with birch pollen rhinitis were examined twice, prior to and late into a Swedish birch pollen season. Ten healthy subjects were examined once. A nasal pool device was used to fill the unilateral nasal cavity with fluid containing 1-deamino-8-D-arginine vasopressin (desmopressin, 20 micrograms/ml) as absorption tracer. The peptide tracer solution was removed after 15 min, and absorption was determined by analysis of the peptide in the 24-h urine sample. Nasal absorption did not differ between healthy subjects and symptom-free patients outside the season. After 3 wk of symptom-producing seasonal allergic rhinitis, absorption of the peptide across the nasal mucosa was less (p < 0.05) than outside the season. These data indicate that hyperresponsiveness and disease progression in seasonal allergic rhinitis are not due to a compromise of the mucosal barrier that would permit increased absorption of mucosally deposited solutes. The reduced absorption may in part reflect the ability of the airway epithelium in vivo to maintain and potentially improve its barrier function by efficient epithelial restitution processes.

Absorption↗

Evidence of potential regulation by interleukin-4 of the soluble intercellular adhesion molecule 1 level in patients with seasonal allergic rhinitis under provocation by a small amount of natural allergen.

Interleukin-4 (IL-4) and intercellular adhesion molecule 1 (ICAM-1) are assumed to be involved in the pathogenesis of allergic disease. In this study, we examined the potential link between IL-4 and soluble ICAM-1 (sICAM-1) levels in patients with allergic rhinitis. The levels of sICAM-1 and IL-4 in sera and in nasal epithelial lining fluids (ELF) from 12 patients with Japanese cedar pollinosis were measured preseason through postseason, and the results were compared with those from 7 healthy subjects. In sera from the allergic subjects, the levels of sICAM- 1 were upregulated during the early part of the season and downregulated during the middle of the season, with upregulation of the IL-4 levels. Moreover, a negative correlation was found between the serum sICAM-1 levels and serum IL-4 levels during the middle (r = -.80) and late (r = -.73) parts of the season. In ELF from allergic subjects, the levels of sICAM-1 were significantly upregulated during the early and middle parts of the season, and began to be downregulated during the late part of the season, with upregulation of the levels of IL-4. In conclusion, IL-4 possibly acts as a potential suppressor of sICAM-1 in the pathogenesis of seasonal allergic rhinitis, at least under provocation by a small amount of natural allergen.

Adult↗

Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure.

Despite the fact that extensive degranulation is a likely prerequisite for a pathogenic role of eosinophils, little is known about the degranulation status of these cells in eosinophilic conditions. The present study of the ultrastructure of tissue eosinophils explores eosinophil degranulation in allergic rhinitis before and during seasonal allergen exposure. A total of 23 patients scored symptoms q.d., prior to and during the pollen season. The numbers of mucosal eosinophils and their degranulation status were determined in nasal biopsies. Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and alpha2-macroglobulin were assessed as indices of eosinophil activity and plasma exudation, respectively. Seasonal allergen exposure was associated with increased nasal symptoms, increased lavage fluid levels of ECP and alpha2-macroglobulin, and increased numbers of tissue eosinophils. In the tissue, transmission electron microscopy revealed a moderate piecemeal degranulation already prior to the season (mean+/-sd 37+/-2.7% altered granules). Seasonal allergen exposure increased this degranulation (87+/-1.8%), and produced local areas with extensive deposition of granule proteins. The degree of eosinophil degranulation correlated with levels of ECP in lavage fluids obtained at histamine challenge. In conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis features moderately degranulated eosinophils already at nonsymptomatic baseline conditions. In association with the development of symptomatic seasonal allergic rhinitis, the tissue deposition of eosinophil granule proteins is dramatically elevated through increased eosinophil numbers, together with markedly augmented degranulation of individual cells.

Adult↗

Multi-omics unveils seasonal remodeling and metabolic crosstalk between testis and abdominal fat body in a non-amplexus stream frog Nanorana taihangnica (Anura: Dicroglossidae).

BACKGROUND: Energy allocation between reproduction and survival represents a fundamental life-history challenge for animals in seasonal environments. Using integrated transcriptomics and metabolomics, we investigated Nanorana taihangnica (Anura: Dicroglossidae), a non-amplexus stream frog endemic to China, to elucidate the seasonal morphological and molecular coordination between the testis and abdominal fat body. RESULTS: Morphological analysis showed that fat body adipocyte cross-sectional area minimized at the end of the breeding season but rapidly recovered thereafter, while testicular volume continued declining post-breeding and only recovered during the non-breeding period. During breeding season, multi-omics analyses revealed that the fat body enhanced fatty acid oxidation, upregulated histidine-carnosine metabolism, activated NAD+ metabolism and FOXO3-mediated antioxidative responses to mitigate metabolic stress, and regulated adipocyte survival and apoptosis via sphingolipid signaling. Seasonal testicular development was centrally regulated by the mTOR signaling pathway, whose activity integrated autophagy levels, NAD+ availability, and aspartate metabolism to coordinate spermatogonial proliferation and spermatogenesis. CONCLUSIONS: This study demonstrates that N. taihangnica optimizes seasonal energy storage, allocation, and reproductive investment through molecular and metabolic crosstalk between the fat body and testis, providing empirical insights into the physiological integration of life-history strategies in animals inhabiting fluctuating environments.

Animals↗

Absence of seasonal variation in the phase of the endogenous circadian rhythm in humans.

Humans may be subject to seasonal variations, as evidenced by the existence of seasonal affective disorder (SAD) and midwinter insomnia. However, some recent studies have shown that the seasonal variation in the phase of the circadian rhythm is relatively weak in healthy humans. In the present study, evidence is found that there is no seasonal variation in the phase of the endogenous circadian rhythm at all. Body temperature, cortisol excretion, and subjective alertness of six subjects recorded under constant routine conditions showed no systematic seasonal variation in circadian phases. This finding indicates that secondary zeitgebers blocked or counterbalanced the seasonal variation in the entrainment effect of the natural photoperiod. The human being may live in an environment in which the photoperiod has lost its status of primary zeitgeber.

Adolescent↗

Seasonality, negative life events and social support in a community sample.

BACKGROUND: Seasonal affective disorder (SAD) is now a well-described form of depressive disorder. However, relatively little research has focused upon psychosocial factors and SAD. AIMS: To determine the association between demographic/psychosocial factors and increased reported seasonal patterns of mood disorder (seasonality) and SAD in a community sample in the UK. METHOD: A total of 1250 people, aged between 18 and 64 years, randomly selected from a primary care database were screened for SAD. Those above cut-off underwent diagnostic interview and completed several self-report questionnaires. Multivariate analysis was conducted to determine which variables were significantly associated with increased seasonality. RESULTS: Four factors (having experienced more numerous negative life events, having low levels of social support, being a woman and being non-native) were predictive of higher seasonality. Being a woman was predictive of being diagnosed as a case of SAD. CONCLUSIONS: A new association has been identified between increased seasonality, negative life events and social support. Future research should assess the psychosocial causes or consequences of SAD while continuing to examine the biology of the condition.

Adolescent↗

[Characteristics of hay fever during pollen season with regard to the influence of specific immunotherapy. I. Clinical course and biochemical changes in nasal lavage].

Nasal lavage is a useful tool for monitoring of inflammatory process in pollinosis. In 27 patients with pollen allergy the nasal lavage was performed before, during and after pollen season. The concentration of total protein, albumin and lysozyme were determined in obtained fluid. In one group Pollinex (Bencard) was applied before pollen season, and in the second one--placebo in similar injections. The concentrations of total protein in nasal lavage fluid was significantly lower after the pollen season in both analyzed groups. On the other hand, the concentrations of albumin and lysozyme were increased during pollen season relatively to values before and after the season. In patients treated with Pollinex observed values after the season were lower than in placebo group.

Adult↗

Seasonal symptoms in the sub-Arctic.

To obtain information regarding the frequency and severity of seasonal symptoms in the sub-Arctic, 361 Seasonal Pattern Assessment Questionnaires (SPAQ) were collected from four separate populations, all either assigned to Fort Wainwright, in Interior Alaska, or receiving treatment there. The study included both civilian and military personnel, of both genders, over 16 years of age. The mean score on the SPAQ was in the low end of the range of sub-syndromal seasonal affective disorder. Females scored significantly higher than males, the mean score approaching that found in seasonal affective disorder. Active duty females scored higher than civilians, and were found to have symptoms severe enough to qualify as true seasonal affective disorder in 10.9% of cases. The highest scores and highest rates of true seasonal affective disorder were found in a group of 25 Medical Activity (MEDDAC) female non-commissioned officers who were not in patient status.

Adolescent↗

The nutritional impact of seasonality in children and adults of rural Ethiopia.

A survey of the nutritional status of subsistence farmers was conducted over 13 months in a rural area of Ethiopia characterized by moderate climatic seasonality and intensive land exploitation. Bi-monthly questionnaires on food consumption, time allocation, agricultural production and cash flow were administered to 203 households and anthropometry performed on 1407 individuals. Comparison of post-harvest and pre-harvest anthropometry was made on 672 individuals (48% of the sample). In children, seasonal changes in the Z-score of weight-for-height were small and not significant. Height growth velocity showed instead a marked seasonal pattern, with values close to normal (-0.2 SD units) in July to December, a period characterized by better food availability, and lower values (-3.0 SD units) in January to June, a period characterized by intensive farm labour and heavy rains. Among the adults, body weight was highest in the post-harvest season (December) and decreased by 1.5 +/- 2.3 kg in men and 1.3 +/- 2.6 kg in women to the yearly minimum in the pre-harvest season (June). The paper shows that in this area children and adults both suffer from exposure to seasonal energy stress. The change in weight-for-height Z-score observed in children and the body weight loss observed in adults was greater in individuals of low socio-economic status and, within the same socio-economic level, in individuals with better nutritional status.

Adolescent↗

Seasonal variation in immediate skin test reactions.

Seasonal variation in the size of immediate prick skin tests was examined in relation to changes in seasonal pollen exposure. Immediate skin test reactions to serial 5-fold dilutions of: (1) a specific pollen during its season (short ragweed), (2) a specific pollen from an earlier season (tree), (3) a perennial allergen (D farinae, D pteronyssinus, or cat), and (4) histamine were examined at the projected trough of ragweed-specific IgE (2nd week in July), at the peak ragweed pollen count (3rd week August), at the estimated peak in ragweed-specific IgE (4th week in September) and at a time of no pollen exposure (2nd week in February). All 30 subjects had symptoms of rhinitis during the ragweed season and a 3 mm or greater wheal to: 100,000 AU/mL of short ragweed, 1:20 wt/vol of a tree exact, and a perennial allergen either 100,000 AU/mL of cat or 10,000 AU/mL of D farinae or D pteronyssinus. The median equivalent dose (dose of skin test material required to produce the median skin test index score) for the four time periods revealed significant seasonal differences. The reactions in October and February were significantly greater than those in July and August for all skin test agents. Histamine, ragweed, and trees showed maximal sensitivity in October, while perennial allergens demonstrated a peak in skin test sensitivity during mid-February.

Adult↗

[Inhibition of histamine liberation in allergic rhinoconjunctivitis in relation to the season].

An increased activity of the cAMP-degrading enzyme phosphodiesterase (PDE) has been observed in peripheral leukocytes from atopic patients. We studied 9 patients with seasonal allergic rhinoconjunctivitis and 9 controls during (summer) and out of symptomatic season (following winter). Dextran sedimented peripheral mixed leucocytes (pML) were preincubated with the nonspecific PDE inhibitor isobutyl-methylxanthine (IBMX), with the PDE III selective inhibitor motapizone and with the PDE IV selective inhibitor rolipram and subsequently histamine release was induced by anti-IgE antibodies. The anti-IgE induced histamine release (anti-IgE HR) showed no significant seasonal differences in atopic patients and in controls. All PDE inhibitors reduced anti-IgE HR over the whole investigated concentration range (from 10(-8) mol/l to 10(-4) mol/l) in a dose dependent manner. Comparing the PDE inhibitors rolipram was the most potent inhibitor on anti-IgE HR from pML of acute and symptomless patients, while there were no significant differences on anti-IgE HR from pML of controls. During symptomatic season rolipram inhibited anti-IgE HR from pML of patients significantly more efficient than out of season. This could be the result of a seasonal increased PDE IV activity in the pMI of patients with allergic rhinoconjunctivitis.

Adult↗

[Seasonal changes of laboratory data in patients with Japanese cedar pollinosis].

Japanese cedar pollen (JCP) causes a significant seasonal allergic rhinitis in Japan during the early spring. Blood samples were collected monthly from October 1993 through October 1994 from 11 patients with Japanese cedar pollinosis. The patients were segregated into two categories based on specific IgE (RAST): single positive RAST to JCP only and multiple positive RAST to JCP, house dust (H1) and mite (D1). These two populations differed in levels of total serum IgE, numbers of eosinophils, basophils and neutrophils in peripheral blood and clinical symptoms. Seasonal increase of JCP-specific IgE was observed after pollen season in both groups. In the single positive group, but not in the multiple positive group, seasonal increase of the number of eosinophils in peripheral blood was observed with post seasonal fall and the level of total serum IgE was increased in the same manner as that of the JCP specific IgE. Although it was not significant, there was a broad seasonal increase of serum nitrate anion, a metabolite of nitric oxide.

Adult↗

Excess mortality due to pneumonia or influenza during influenza seasons among persons with acquired immunodeficiency syndrome.

BACKGROUND: Anecdotal reports suggest that influenza-related morbidity may be high among persons with acquired immunodeficiency syndrome (AIDS), but little information is available concerning the population-level impact of influenza on mortality in persons with AIDS. METHODS: Using the Multiple Cause-of-Death data files, which contain information on all deaths occurring in the United States each year, we calculated the numbers of excess deaths and rates of excess death due to pneumonia or influenza among persons with AIDS aged 13 years and older during the influenza seasons 1991-1992 through 1993-1994. For comparison, numbers of excess deaths and excess death rates were also calculated for several other groups including the general US population aged 13 years and older and the general US population aged 65 years and older. RESULTS: During the 1991-1992, 1992-1993, and 1993-1994 influenza seasons, there were 261, 254, and 191 excess deaths due to pneumonia or influenza in persons with AIDS and excess death rates of 19.74, 15.38, and 10.17 deaths per 10 000 persons, respectively, compared with a summer baseline period. For the same seasons, we observed excess death rates of 1.40, 1.62, and 1.48 for the general US population aged 13 years and older and 8.10, 9.28, and 8.54 for the general US population aged 65 years and older. Thus, persons with AIDS had excess death rates substantially higher than the general US population and similar to, if not somewhat higher than, the general US population aged 65 years and older, a group that is already targeted for annual vaccination. The findings were similar when we compared the preinfluenza season with the influenza season. CONCLUSIONS: Persons with AIDS have significant excess mortality due to pneumonia or influenza during influenza seasons and should be considered a high-risk group that is targeted for the prevention of influenza.

Acquired Immunodeficiency Syndrome↗

Roles of photoperiod and testosterone in seasonal plasticity of the avian song control system.

The song control nuclei of songbirds undergo pronounced seasonal changes in size and neuronal attributes. The mechanisms by which seasonal changes in environmental variables such as photoperiod mediate seasonal changes in these brain regions are not known. Manipulations of photoperiod and/or testosterone in captive songbirds induce seasonal changes in the size of song nuclei comparable to those observed in wild songbirds. It is unclear, however, whether the effects of photoperiod on the song nuclei are mediated by testosterone or by steroid-independent mechanisms. We independently manipulated photoperiod and testosterone in castrated male Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) to determine the contributions of steroid-dependent and -independent actions of photoperiod to seasonal changes in the size and neuronal attributes of song nuclei. Testosterone implants increased the size of several song nuclei, regardless of photoperiod. Photoperiod exerted small but significant steroid-independent effects on the volume of the higher vocal center and the size of neurons in the robust nucleus of the archistriatum. Photoperiod also modulated the effect of testosterone on the size of area X; testosterone treatment had a more pronounced effect on the size of area X on short days than on long days. These results suggest that although testosterone is the primary factor mediating seasonal changes in neural attributes of the song nuclei, photoperiod may act via mechanisms that are independent of steroid levels to supplement or modulate the actions of testosterone.

Animals↗

Vocal control region sizes of an adult female songbird change seasonally in the absence of detectable circulating testosterone concentrations.

Previous research established that in several species of seasonally breeding oscine birds, brain areas [vocal control regions (VCRs)] that control vocal behavior learning and expression exhibit seasonal plasticity, being larger during than outside the reproductive period. In adult males, this seasonal decrease correlates with circulating testosterone (T) concentrations. VCRs contain androgen receptors and T plays an important role in neural plasticity and in the control of singing behavior. In behaviorally dimorphic species, VCRs are larger in males than females and change seasonally also in females, but the dependency of these changes on circulating T levels in females has not been established. In free-living adult dark-eyed juncos (Junco hyemalis), a species in which females do not normally sing, the sizes of three VCRs (high vocal center, robust nucleus of the archistriatum, and Area X) were larger in males than females and decreased between summer and fall in both sexes. In males, this decrease was associated with changes in circulating T concentrations. Females, however, had on average undetectable T levels throughout the breeding season. Seasonal changes in VCR volumes in adult females may depend on very low (below detection limit) circulating T concentrations, on nonandrogenic plasma steroids, on androgen (or androgen metabolites) produced in brain tissues, and/or on nonsteroidal factors such as photoperiod or social interactions with conspecific birds.

Analysis of Variance↗