The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action-eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen-immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.

Use of inhaler devices in pediatric asthma.

Inhalation is the preferred route for asthma therapy, since it offers a rapid onset of drug action, requires smaller doses, and reduces systemic effects compared with other routes of administration. Unfortunately, inhalation devices are frequently used in an empirical manner rather than on evidence-based awareness.A wide variety of nebulizers are available. Conventional jet nebulizers are highly inefficient, as much of the aerosol is wasted during exhalation. However, incorporating an extra open vent into the system has considerably increased the amount of drug that patients receive. Breath-assisted open vent nebulizers limit the loss of aerosol during exhalation, but are dependent on the patient's inspiratory flow. Ultrasonic nebulizers produce a high mass output and have a short nebulization time, but are inefficient for delivering suspensions or viscous solutions. Adaptive aerosol delivery devices release a precise dose that is tailored to the individual patient's breathing pattern. Nebulizers have several drawbacks, and their use should be limited to patients who cannot correctly manage other devices.Pressurized metered-dose inhalers (pMDI) are practical, cheap and multidose. However, there are several problems with their use. Breath-actuated MDI are easy to use and can be activated by very low flow. However, young children may not be able to use them efficiently. Dry powder inhalers (DPI) are portable and easy to use. They are indicated either for rescue bronchodilator therapy or for regular treatment with inhaled corticosteroids and long-acting bronchodilators. The use of spacers reduces oropharyngeal deposition and improves drug delivery to the lung. Spacers do not require patient coordination, but some general rules must be followed for their optimal use.Thus, the choice of a delivery device mainly depends on the age of the patient, the drug to be administered and the condition to be treated. Proper education is also essential when prescribing an inhalation device.

Cough, wheezing and asthma in children: lesson from the past.

Recurrent cough is an important medical and sometimes frustrating problem encountered by pediatricians, especially if it is not associated with wheeze or other evidence of systemic disease. In the past, many children with chronic cough have been diagnosed as asthmatic. However, epidemiological, clinical and laboratory studies conducted over the last ten years elucidated many aspects of the relationship between cough and bronchoconstriction. It is difficult to make a diagnosis of asthma on cough alone, but the setting in which the patient is seen (i.e., in a primary care setting or ain a specialistic clinic) may address doctors to the right diagnosis. A prudent ''wait and see'' approach may be useful in many occasions.

Does cognitive dysfunction conform to a distinctive pattern in obstructive sleep apnea syndrome?

Obstructive sleep apnea (OSA) is a recognized cause of cognitive dysfunction. By using a cross-sectional comparative study, we aimed to verify whether neuropsychological performance of untreated OSA patients conforms to a distinctive pattern. Forty-nine newly diagnosed, untreated OSA patients, 27 with multi-infarctual dementia (MID), 31 with mild to moderate dementia of Alzheimer type (DAT) and 63 with severe chronic obstructive pulmonary disease (COPD), all free from major comorbid dementing conditions were chosen for the study. The groups were matched for age and education. We found a bimodal distribution of cognitive performance in OSA group, which was therefore divided into two clusters having better (OSAb, n = 35) and worse (OSAw, n = 14) performance on a battery of 10 cognitive indexes. Cognitive performances of OSAb, OSAw, MID, DAT and COPD were compared by discriminant analysis. OSAb performed better than OSAw in all but one test. Deductive thinking and verbal attainment were more severely impaired in OSAw than in COPD patients. Constructive ability, deductive thinking and both verbal attainment and immediate memory were comparably impaired in OSAw and DAT. The mean neuropsychological scores of OSAw and MID were comparable, but 71% of OSAw patients had a distinctive cognitive profile, i.e. a group specific pattern of cognitive dysfunction, according to discriminant analysis. One of four newly diagnosed OSA patients had a severe and distinctive neuropsychological dysfunction mainly involving inductive and deductive thinking, and constructive ability. Some analogy with cognitive pattern of MID suggests that a mainly subcortical damage underlies this dysfunction.