Psychological Stress, Lung Function and Exacerbation Risk in COPD: Is an Increase of Cholinergic Tone a Possible Link?

at a glance: On the hypothesis that psychological distress might interfere with airway reactivity in patients suffering of mild to moderate COPD through a cholinergic-mediated-bronchial reflex.

Direct and indirect exposure to horse: risk for sensitization and asthma.

Most studies on the sensitization to horse allergens in populations without professional exposure have been carried out in geographical areas where the rate of horse ownership is high and horse riding is popular. Very few studies have been carried out in populations living in large urban areas. This gap in the literature probably reflects the widespread view that prevalence of horse-related allergy is low in urban populations because the latter are not regularly exposed to horses. On the contrary, we suggest that urban areas constitute a model useful to study potential modalities of exposure and sensitization to horse allergen by other routes of exposure than horse-riding. In this article, we describe the risks related to various modalities of exposure to horse allergen, clinical aspects of airway sensitization to horse allergens in patients living in urban areas, and non-occupational exposure to horse allergen. In addition, we illuminate some aspects related to dispersion of horse allergens from sources such as stables to indoor environments.

Bronchial asthma.

PURPOSE OF REVIEW: The aim of this review is to underline the need for an adequate clinical and functional evaluation of respiratory function and asthma control in patients undergoing surgical procedures requiring general anesthesia to obtain useful information for an adequate preoperative pharmacological approach. RECENT FINDINGS: It has been shown that baseline uncontrolled clinical/functional conditions of airways represent the most important risk factors for perioperative bronchospasm. In nonemergency conditions, asthma patients should undergo clinical/functional assessment at least 1 week before the surgery intervention to obtain, the better feasible control of asthma symptoms in the single patient. Some simple preoperative information given by the patient in preoperative consultation may be sufficient to identify individuals with uncontrolled or poor controlled asthmatic conditions. Spirometric evaluation is essential in individuals with poor control of symptoms, as well as in those patients with uncertain anamnestic data or limited perception of respiratory symptoms, and in those requiring lung resection. SUMMARY: A better control of asthma must be considered the 'gold standard' for a patient at 'a reasonable low risk' to develop perioperative/postoperative bronchospasm. International consensus promoted by pulmonologists, anesthesiologists, and allergists might be useful to define a better diagnostic and therapeutic approach.

Can bronchial asthma with an highly prevalent airway (and systemic) vagal tone be considered an independent asthma phenotype? Possible role of anticholinergics.

Recently, we studied occurrence and role of non-respiratory symptoms (n-RSs) before a worsening of asthma symptoms. Some n-RSs such as anxiety, reflux, heartburn, abdominal pain, which appeared within 3 h before the onset of an asthma attack, are the likely result of an imbalance between sympathetic/parasympathetic systems with an increase in cholinergic tone. Therefore, it is likely that some of these n-RSs induced by the increased cholinergic tone might be present related with specific parasympathetic-associated respiratory symptoms such as those elicited by airway narrowing. It is likely that, at least in some categories of asthmatics, an increased cholinergic tone, rather than other well-known factors, might play a prevalent role in triggering bronchospasm. If this is the case, it is possible to speculate that the use of anticholinergic agents (mainly those with long-acting activity) in patients suffering from asthma should be more beneficial in individuals characterized by a higher degree of cholinergic tone that, consequently might be the ideal target for the use of long-acting anticholinergics and, possibly, represent a novel asthma phenotype. The presence of parasympathetic-associated n-RSs might help the physician to identify this type of patients, although this might be followed by a more detailed assessment.

Bronchodilator response to formoterol after regular tiotropium or to tiotropium after regular formoterol in COPD patients.

We conducted a randomized, crossover trial with tiotropium 18 microg once daily (group A), and formoterol 12 microg twice daily (group B) over a 5-day period for each drug, with a 10-day washout, in 20 COPD patients. At the end of each period, patients inhaled both drugs separated by 180 min in alternate sequence (group A: tiotropium 18 microg+formoterol 12 microg; group B: formoterol 12 microg+tiotropium 18 microg). FEV1 and FVC were measured at baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. FEV1 and FVC further improved after crossover with both sequences. The mean maximal change in FEV1 over baseline was 0.226 L (0.154-0.298) after tiotropium+formoterol and 0.228 L (0.165-0.291) after formoterol+tiotropium; the mean maximal change in FEV1 over pre-inhalation the second drug value was 0.081 L (0.029-0.133) after tiotropium+formoterol and 0.054 L (0.016-0.092) after formoterol+tiotropium. The mean maximal change in FVC over baseline was 0.519 L (0.361-0.676) after tiotropium+formoterol and 0.495 L (0.307-0.683) after formoterol+tiotropium; the mean maximal change in FVC over pre-inhalation of the second drug value was 0.159 L (0.048-0.270) after tiotropium+formoterol and 0.175 L (0.083-0.266) after formoterol+tiotropium. The FEV1 AUCs(0-360 min) were 62.70 (45.67-79.74) after tiotropium+formoterol and 69.20 (50.84-87.57) after formoterol+tiotropium, the FEV1 AUCs(0-180 min) were 24.70 (18.19-31.21) after tiotropium+formoterol and 29.74 (21.02-38.46) after formoterol+tiotropium, whereas the FEV1 AUCs(180-360 min) were 15.70 (10.88-20.52) after tiotropium+formoterol and 11.71 (7.21-16.21) after formoterol+tiotropium. Differences between the two treatments were not statistically significant (P>0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage.

Treatment of acute exacerbation of severe-to-very severe COPD with azithromycin in patients vaccinated against Streptococcus pneumoniae.

Sixty-five consecutive eligible adult patients, who were treated as outpatients for stable severe-to-very severe COPD, were enrolled in the study. All of them received 23-valent pneumococcal capsular polysaccharide vaccine intramuscularly. Patients were seen monthly, as well as whenever they had symptoms suggestive of an exacerbation, at our outpatient clinic. Eighteen out of 65 patients suffered from acute exacerbation (AECOPD). Three of these patients presented two episodes of AECOPD. Patients with an acute exacerbation of COPD received azithromycin 500 mg/day once daily for 3 days and a short course of oral prednisolone 25 mg/die. In 16 cases, a single species was isolated, while in the remaining 5 cases at least two species were recovered. Clinical cure or improvement at the end of therapy (3-5 days post-therapy) was reported in 17 episodes of AECOPD with no relapse at the late post-therapy (10-14 days after the completion of treatment). Bacteriologic eradication or presumptive eradication rates at the end of therapy were 86% (24 out of 28 isolates). Azithromycin eradicated all isolates of Haemophilus influenzae, Moraxella catarrhalis, H. parainfluenzae, Klebsiella pneumoniae, and Klebsiella spp. isolated at baseline. Eradication of Sta aureus occurred in 1 of 3 isolates whereas azithromycin was unable to eradicate Pseudomonas aeruginosa isolates. Our data seem to indicate that pneumococcal vaccination reduces the possibility that an AECOPD is caused by Streptococcus pneumoniae. This finding allows the use of antibiotics such as azithromycin, which, otherwise, should be avoided because of resistances.

The effect of pet ownership on the risk of allergic sensitisation and bronchial asthma.

An increasing volume of evidence suggests that early contact of children with the allergens of furred pets (especially those produced by cats) may determine a lower risk of developing allergic sensitisation to these materials. A possible explanation of this data is that an early inhalation of high levels of the major cat allergen Fel d 1 induces the production of IgG and IgG4 antibodies with a "protective" effect. Other authors have shown that the prevalence of allergic sensitisation to cats, in adults, is reduced in those patients exposed to the lowest and highest levels of the allergens. On the contrary, the risk of developing sensitisation to cats is significantly higher when the patients were exposed to intermediate levels of Fel d 1. Moreover, epidemiological studies have demonstrated a relatively low prevalence of cat allergy (about 10%) in some countries where rates of cat ownership are high. This data confirms the role of indirect exposure to pet allergens in inducing allergic sensitisation. Clothes of pet owners have been indicated as the carriers for the dispersal of these allergens in pet-free environments. However, it is important to point out that exposure of highly sensitised patients to relevant amounts of pet allergens (such as in a pet shows/shops) may determine a dramatic exacerbation of nasal and/or bronchial symptoms.

Safety of celecoxib in patients with adverse skin reactions to acetaminophen (paracetamol) and nimesulide associated or not with common non-steroidal anti-inflammatory drugs.

BACKGROUND: Acetaminophen (paracetamol--P) and Nimesulide (N) are widely used analgesic-antipyretic/anti-inflammatory drugs. The rate of adverse hypersensitivity reactions to these agents is generally low. On the contrary non-steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in such reactions. Celecoxib (CE) is a novel drug, with high selectivity and affinity for COX-2 enzyme. OBJECTIVE: We evaluated the tolerability of CE in a group of patients with documented history of adverse cutaneous reactions to P and N associated or not to classic NSAIDs. METHODS: We studied 9 patients with hypersensitivity to P and N with or without associated reactions to classic NSAIDs. The diagnosis of P and N-induced skin reactions was based in vivo challenge. The placebo was blindly administered at the beginning of each challenge. After three days, a cumulative dosage of 200 mg of CE in refracted doses were given. After 2-3 days, a single dose of 200 mg was administered. All patients were observed for 6 hours after each challenge, and controlled again after 24 hours to exclude delayed reactions. The challenge was considered positive if one or more of the following appeared: erythema, rush or urticaria-angioedema. RESULTS: No reaction was observed with placebo and eight patients (88.8%) tolerated CE. Only one patient developed a moderate angioedema of the lips. CONCLUSION: Only one hypersensitivity reaction to CE was documented among 9 P and N-highly NSAIDs intolerant patients. Thus, we conclude that CE is a reasonably safe alternative to be used in subjects who do not tolerate P and N.