Studies on the relationships between sensitivity to cold, dry air, hyperosmolal solutions, and histamine in the adult nose

We have previously reported that elevated osmolality of nasal secretions is linked to the rhinitic reaction to cold and dry air (CDA) that results in inflammatory mediator release and that nasal challenge with hyperosmolal solutions can induce histamine release in randomly selected individuals. These findings led to a comparison of the effect of nasal challenge with hypertonic fluid in 11 subjects who demonstrated a nasal response to CDA compared to 10 subjects without CDA sensitivity. All volunteers were challenged with isosmolal (300 mosmol/kg H2O) and hyperosmolal (800 mosmol/kg H2O) mannitol solutions. Their response was evaluated by symptom scores and quantification of histamine in nasal lavages. CDA responders differed significantly from non-responders in terms of both the total amount and the concentration of histamine in the lavage following hyperosmolal challenge (p less than 0.04 and p less than 0.02, respectively). In addition, CDA responders reported a higher change from baseline for nasal congestion, pruritus, and lacrimation following hyperosmolal challenge, but the scores for rhinorrhea, the volume of the returned nasal lavage fluid following hyperosmolal challenge, and the capacity to reduce the osmolality of the administered hyperosmolal fluid did not differ. Allergic status was not a factor in hyperosmolal reactivity. To investigate possible differences in nonspecific nasal mucosal sensitivity that could account for these findings, all subjects underwent provocation with five increasing doses of histamine, from 0.01 to 1 mg. No significant difference between CDA responders and nonresponders in symptomatology or in the induction of vascular permeability, as assessed by TAME-esterase activity in nasal fluids, could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)     

The impact of age on prevalence of positive skin prick tests and specific IgE tests

Aging is associated with modifications of the immune system, defined as immunosenescence. This could contribute to a reduced prevalence of allergic disease in the elderly population. In this regard, atopy has rarely been considered in the clinical assessment of the geriatric respiratory patient. This article is a review of the available literature assessing the impact of age on atopy. In the majority of papers, we found a lower prevalence of atopy in the most advanced ages, both in healthy subjects and in individuals affected by allergic respiratory diseases. Unfortunately, no large, longitudinal studies performed in the general population have been conducted to further explore this observation. Although available data seem to favor the decline of allergen sensitization with age, the prevalence of allergic sensitizations in the elderly population with respiratory symptoms is substantial enough to warrant evaluation of the atopic condition. From a clinical perspective, allergic reactions in older adults can have the same or even worse manifestations compared to young people. For this reasons, the evaluation of the atopic condition also in the geriatric patient is recommended. Thus, the role of atopy as it pertains to the diagnosis, therapy (adoption of preventive measure such as removal of environmental allergen or immunotherapy), and prognosis (influence on morbidity and mortality) of chronic respiratory illnesses in the elderly is addressed.     

Familial C3 Glomerulopathy Associated with CFHR5 Mutations: Clinical Characteristics of 91 Patients in 16 Pedigrees

Summary

Background and objectives

Complement factor H and related proteins (CFHR) are key regulators of the alternative complement pathway, where loss of function mutations lead to a glomerulopathy with isolated mesangial C3 deposits without immunoglobulins. Gale et al. (12) reported on 26 patients with the first familial, hematuric glomerulopathy caused by a founder mutation in the CFHR5 gene in patients of Cypriot descent living in the United Kingdom. CFHR5 nephropathy is clinically characterized by continuous microscopic hematuria whereas some patients present with additional episodes of synpharyngitic macrohematuria, associated with infection and pyrexia. A subgroup of patients, particularly men, develop additional proteinuria, hypertension, and chronic renal disease or ESRD.

Design, setting, participants, & measurements

We herewith expand significantly on the study by Gale et al., reporting on histologic, molecular, and clinical findings in 91 patients from 16 families with the same founder mutation.

Results

Eighty-two patients (90%) exhibited microscopic hematuria; 51 (62%), exhibited only microscopic hematuria, whereas the remaining 31 additionally had proteinuria (38%); 28 proteinuric patients developed chronic renal failure (CRF). Among carriers of CFHR5 mutation aged >50 years, 80% of the men and 21% of the women developed CRF; 18 developed ESRD (14 men [78%], 4 women [22%]).

Conclusions

The diagnosis of CFHR5-related, isolated C3 glomerulopathy was established in 2009 using newly described mutation analysis after decades of follow-up with unclear diagnoses, occasionally confused with IgA nephropathy. This larger patient cohort establishes the clinical course, significant variable expressivity, and marked gender difference regarding the development of CRF and ESRD.