Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways.

To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. We show that this regimen induced remarkably high and stable lung T-cell responses in nonhuman primates and that it also generated systemic and respiratory tract humoral responses of both IgA and IgG isotypes. Moreover, strong immunogenicity was achieved even in animals with preexisting antiadenoviral immunity, overcoming a critical hurdle to the use of these vectors in humans, who commonly are immune to adenoviruses.

The immunogenicity profile elicited with this regimen, which is distinct from either intramuscular or intranasal delivery, has highly desirable properties for protection against respiratory pathogens. We show that it can be used repeatedly to generate mucosal humoral, CD4, and CD8 T-cell responses and as such may be applicable to other mucosally transmitted pathogens such as HIV. Indeed, in a lethal challenge model, we show that aerosolized recombinant adenoviral immunization completely protects ferrets against H5N1 highly pathogenic avian influenza virus. Thus, genetic immunization in the lung offers a powerful platform approach to generating protective immune responses against respiratory pathogens.

This is an updated overview of indications, contraindications, performance and interpretation of bronchial challenge tests. As speciality, the diagnostic step by step scheme comprises in addition to the clinical case history a detailed exposure (occupational) history, lung function testing, assessment of nonspecific bronchial hyperresponsiveness, allergological diagnostics (skin prick test, measurement of specific IgE antibodies), privation and reexposure test and as gold standard specific bronchial challenge tests. The last mentioned tests are of particular importance in the framework of a diagnostic backup with regard to specific therapeutic and preventive measures and insurance regulations (occupational disease?).

Specific bronchial challenge tests and their variant, the workplace-related challenge test, serve to objectify or exclude the clinical relevance and the current state of a respiratory sensitization. They require a comprehensive experience of the physician performing the tests. The majority of diseases does not necessitate these tests, especially if case history, lung function testing, allergy tests, privation and reexposure test provide unanimously positive results. If allergic symptoms of conjunctiva or the upper respiratory tract are of prime importance the performance of a specific conjunctival or nasal challenge test is recommended.

Asthma is a disease of the lung epithelial barrier, most often associated with allergy in children. Asthma and allergy are two distinct diseases, but the phenotypic expression of asthma depends on atopic status. A better definition of phenotypes of asthma would result in better targeting of prevention and treatment modalities. Secondary prevention aims to prevent the onset of asthma and the acquisition of new sensitizations in sensitized children.

Studies concerning allergen avoidance are insufficient to reach a definitive conclusion and antihistamines have not been shown to be effective. The results for specific immunotherapy suggest a benefit to prevent transition from allergic rhinitis to asthma and the onset of new sensitizations. Tertiary prevention aims to reduce symptoms in children with an existing allergic asthma diagnosis. The avoidance of known respiratory allergens will only be effective in combination with management of the whole environment. Specific immunotherapy has a real place, in combination with background therapy. It should be used according to guidelines in appropriately treated patients.

Sublingual immunotherapy (SLIT) was introduced in the treatment of respiratory allergy as an option to subcutaneous immunotherapy (SCIT), which is clinically effective but has the problem of adverse systemic reactions, quite rare but sometimes life-threatening. A large number of trials, globally evaluated in several meta-analyses, demonstrated that SLIT is an efficacious treatment for allergic rhinitis and allergic asthma and has a satisfactory safety profile, severe reactions being extremely rare, though an increased risk is apparent in subjects undergoing SLIT because of previous systemic reactions to SCIT.

The suitability of SLIT is ensured by a good compliance, higher than reported for SCIT, the injections being a major factor for noncompliance with the latter, and by its cost-effectiveness performances. In fact, a number of studies showed that SLIT may be very beneficial to the healthcare system, especially after its stopping, when there is no more the cost of the treatment but its efficacy on symptoms persists.