Impact of chlorinated swimming pools attendance on the respiratory health of adolescents
Hyper IgE syndrome (Buckley’s Syndrome)
Domestic use of Hypochlorite Bleach , Atopy and Respiratory Symptoms in Adults
The eosinophil and its novel functions
Asthma and Influenza A (H1N1)
Are asthmatic patients more prone to developing severe forms of this pandemic influenza which affects all the world population in 2009 ?
This is the question we may ask upon reading the preliminary report carried out during the Spring2009, in the US, involving 13,217 cases registered between May and June, of which 1082 were hospitalized. Among them data were collected on 272 patients admitted for at least 24h with symptoms of influenza-like illness (fever and cough), the diagnosis of H1N1 being confirmed by RT-PCR (S. Jain et al. NEJM 2009 ; 361 : 1935-1944)
45% were children or adolescents under 18 years of age, and 5% were adults older than 65years of age. 67 were admitted to an Intensive Care Units and 19 died
But the most striking observation was that 73% of the patients had underlying medical conditions and the illness which was, by far, the most frequent was Asthma , both in children (35cases; 29%) and adults (41 cases; 27%). Moreover 86 individuals out of 239 received corticosteroids, half of them for asthma.
However, the majority of patients (253; 93%) were able to leave hospital after having received anti-viral treatment (Oseltamivir (Tamiflu®) or Zanamivir Relenza®) which was more beneficial if given in the first 3 days after the onset of symptoms. This US survey, although partial and limited in time, must be taken into account by European Asthma and Allergy specialists and justify in asthmatic patients affected with H1N1 virus, an early administration of antiviral treatment, or even better, preventive measures, particularly vaccination.
In this respect, let us underline the comprehensive analysis performed by J.M. Kelso and J.T. Li, on the side-effects of all known vaccines (Ann. Allergy Asthma and Immunol. 2009; 103 (4, Suppl 2) : S2-S12) and highlight “Clinical pearls for preventing, diagnosing and treating seasonal and H1N1 influenzaM. Rank and J.T. Li JACI 2009; 124: 1123-1126) T infection in patients with asthma (he authors recommend use of inactivated trivalent vaccine which has been, until now, perfectly tolerated (like vaccination against seasonal flu), the rare contraindications being egg allergy (if convincingly demonstrated) or serious reactions to previous anti-flu vaccination. Asthmatic patients should be tested by RT-PCR for H1N1, despite the delay and the cost of such a test, when the diagnosis is in question and there is a decision to take about anti-bacterial or anti-viral treatment. Over all, Oseltamivir is preferable to Zanamivir (except in cases of resistance), and particularly if chemoprophylaxis is considered in young asthmatic patient , not yet vaccinated and in close-contact with known influenza cases
Impact of chlorinated swimming pools attendance on the respiratory health of adolescents
In order to address this issue, A. Bernard et al followed up 847 adolescents 13 to 18 years of age. Among them,114 individuals who swam in non-chlorinated swimming pools (sterilized by ionisation with a copper-silver battery) served as a reference group (Pediatrics 2009; 124 : 1110-1118).
The authors took into account the various levels of chloride and outdoor and indoor exposure conditions, as well as the presence of exercise-induced bronchoconstriction (EIB), and different types of respiratory manifestations: hay fever (HF), allergic rhinitis (AR) known or ever asthma (KA), current asthma (CA) or CA associated with EIB.
Among atopic adolescents (with total serum IgE levels > 30 KIU/L or positive aeroallergen-specific IgE levels), the risk of development of asthma in individuals with KA or CA increased with the number of hours spent in a chlorinated atmosphere (OR – 7.1 to 14.9 when such period was > 1000 h) ; a similar situation was seen in terms of risk of developing HF or AR (OR – 3.3 to 6.6 and 2.3 to 3.5, respectively, when the exposure period exceeded 100 h for HF and 1000 h for AR).
Similar results were not observed either in the control group or in the non-atopic population.
The authors concluded that regular swimming in chlorinated pools by adolescents has a deleterious action in atopic individuals, in whom it worsens asthma and other manifestations of respiratory allergy, whereas such negative effect is not observed in non allergic swimmers.
Hyper IgE syndrome (Buckley’s Syndrome)
This is a complex and relatively rare, primary immunodeficiency which may only be revealed on adults and which is characterized by a very important increase in serum IgE, reaching levels between 1200 and 3000 IU/ml , a severe form of atopic dermatitis and a sensitivity to extracellular bacteria, particularly cutaneous staphylococci (furunculosis) and pulmonary infections with pneumatocele formations. In addition, a large number of non-immunological symptoms complete the clinical picture : dysmorphic facial features , hyperextensive joints, , shedding of deciduous teeth, scoliosis and a tendency toward developing bone fractures following minor trauma. Overall, this syndrome is considered to be due to a deficiency of endocytosis and bactericidal capacity of phagocytic cells, closed to to Chronic Granulomatosis and Job’s Syndrome.
A recent genetic study (Y. Minegishi. Curr. Opin. Immunol. 2009 ; 21 : 487-492) demonstrated 2 types of mutations: one in the STAT 3 (Signal Transducer and Activator of Transcription) gene, leading to the classical form of the syndrome, and another « null » mutation of the tyrosine-kinase gene, leading to an autosomal recessive form of the syndrome, associated with viral and mycobacterial infections but without skeletal or dental defects.
There is, in both cases, a deficiency in signal transduction pathways for multiple cytokines, namely IL-6 and IL-23, reflecting a dysfunction of Th17 cells. These cells are a 3rd subtype of effector T helper cells (in addition to Th1 and Th2 cells) .Their role is progressively better known in terms of response to infections and in auto-immunity.
Thus, in Hyper IgE syndrome, the cytokine deficiency constitutes the molecular basis for the immunological and non immunological abnormalities.
Domestic use of Hypochlorite Bleach , Atopy and Respiratory Symptoms in Adults
It is well known that domestic use of Bleach can inactivate allergens and reduce the risk of allergy in children, but also that its professional use in adults may trigger respiratory problems.
European investigators from10 different countries focused upon this problem (J.P. Zock et al. JACI 2009 ; 124 : 731-738) by questioning 3626 adults who used bleach at home and in whom it was possible to test the levels of IgE specific for 4 different common aeroallergens. The authors also measured the concentration of house dust mite and cat allergens in mattress dust. Statistical analysis showed that atopic sensitization (demonstrated by domestic and pollen-related aeroallergen-specific IgE levels) was lower in individuals using bleach and all the more that use of the product was frequent
By contrast, non allergic lower airway manifestations were more frequent among bleach users, particularly when the product was used more than 4 days per week.
Thus, bleach seems to be a double-edged sword, since individuals who clean their homes with bleach are less prone to becoming atopic but more frequently develop respiratory symptoms.
The eosinophil and its novel functions
The eosinophil has always been regarded as the effector cell participating in the immune response involved in allergic inflammation and parasitic infections, thanks to the presence of specific granules in its cytoplasm which contain, among others, MBP (Major Basic Protein), ECP (Eosinophil Cationic Protein) and EPO (Eosinophil Peroxydase). In addition, the eosinophil shows various membrane receptors which allow it to interact with IgE and IgA antibodies.
The eosinophil can also synthesize and secrete cytokines such as IL-5, which acts as its own growth factor and IL-4, which may participate in the regulation of Th1 or Th2 immune responses. The eosinophil releases these cytokines by a process of selective degranulation: thus, activation by IgE induces release of EPO and IL5 but not ECP or INF-gamma.
In addition, as Monique Capron and F. Legrand have shown (Bull. Acad. Med 2009 ; 193 : 2 229-349) the so-called Hypereosinophilic syndrome can be broken down into 2 subtypes based upon the presence of mutations in the myeloid lineage. One is associated with a «myeloproliferative variant »and leads to the development of a fusion protein called Fip1-L1, which has tyrosine-kinase activity, and which can therefore induce cell proliferation and may be amenable to treatment by an inhibitor of this enzyme such as Imatimib or Glivec®. The other variant, the «lymphoid variant» leads to clonal proliferation of abnormal T Lymphocytes producing high amounts of IL-5, which is responsible for the hypereosinophilia.
But the authors go even further and their research showed the presence of membrane receptors linked to Innate immunity on eosinophils, such as lectin-type receptors, which, when triggered provide a signal of danger regarding pathogenic agents.
Thus, we can consider a possible role for the eosinophil, in anti-tumor immune surveillance. Since eosinophils are also found in the core of various cancers (colon, lung, bladder, lymphomas), the authors were able to experimentally show that if eosinophils are associated most frequently with a favourable prognosis (except for Hodgkin’s disease), they have a role , like NK cells and gamma-delta T cells, in induction of apoptosis and even necrosis of certain tumors such as colon cancer. These notions come to the support of t hypothesis put forward a long time ago by many clinicians and epidemiologists suggesting an atopy- cancer antagonism.
