Correlation between bituberous diameter and mode of delivery in a cohort of low-risk nulliparous women.

OBJECTIVE: The aim our study was to evaluate the association between the antepartum clinical measurement of the Bituberous Diameter (BTD) and the occurrence of unplanned obstetrical intervention (UOI) due to labor dystocia, including either operative vaginal delivery or caesarean section in a cohort of low-risk, nulliparous at term. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Tertiary maternity care. INTERVENTIONS: With the women lying in lithotomic the distance between two ischial tuberosities was assessed using a tape measure during the routine antenatal booking between 37 and 38 weeks of gestation. MEASUREMENTS AND FINDINGS: Overall, 116 patient were included, and of these 23(19.8%) were submitted to an UOI due to labor dystocia. Compared to women that had a spontaneous vaginal delivery, women submitted to an UOI had a shorter BTD (8.25 + 0.843 vs 9.60 + 1.12, p < 0.001), a higher frequency of epidural analgesia (21/23 or 91.3% vs 50/93 or 53.8%; p = 0.002) and of augmentation of labor (14/23 or 60.9% vs 19/93 or 20.4%; p < 0.001) as well as a longer first [455 (IQR 142-455 min vs 293 (IQR 142-455) min] and second stages of labor [129 (IQR 85-155) min vs 51 (IQR 27-78) min]. Multivariable logistic regression showed that the BTD (aOR 0.16, 95% CI 0.04-0.60; p = 0.007) and the length of the second stage of labor (aOR 6.83, 95% CI 2.10-22.23; p = 0.001) were independently associated with UOI. When evaluating the diagnostic accuracy of the BTD for the prediction of UOI due to labor dystocia, the BTD showed an AUC of 0.82 (95 %CI 0.73-0.91; p < 0.001) with an optimal cut-off value of 8.6 cm (78.3% (95 %CI 56.3-92.5) sensitivity, 77.4% (95 %CI 67.6-85.4) specificity, 46.2% (95% CI 30.1-62.8) PPV, 93.5% (95% CI 85.5-97.9) NPV, 3.5 (95% CI 2.3-5.4) positive LR, and 0.28 (95% CI 0.13-0.61) negative LR. A significant inverse correlation between the length of the second stage of labour and the BTD in patients that had a vaginal delivery was also demonstrated (Spearman's rho = -0.24, p = 0.01). KEY CONCLUSIONS: Our study suggests that antepartum clinical assessment of the BTD might be used as a reliable predictor of UOI due to labor dystocia in low-risk, nulliparous women at term gestation. IMPLICATIONS FOR PRACTICE: Antenatal identification of women at higher risk for labor dystocia might trigger some interventions during the second stage of labor, such as maternal position shifting, to increase the pelvic capacity and potentially improve outcomes or might prompt a referral of the patient to a district hospital prior to the onset of labor.

LTP allergy/sensitization in a pediatric population.

Plant lipid transfer proteins (LTPs) are widespread plant food allergens, highly resistant to food processing and to the gastrointestinal environment, which have been described as the most common food allergens in the Mediterranean area. LTP allergy is widely described in adults, but it represents an emerging allergen also in the pediatric population. Little is known about the real prevalence and the clinical features of this allergy in children and it still often remains underdiagnosed in these patients. An early identification and a deeper knowledge of this allergy in childhood can avoid severe systemic reactions and improve the child's quality of life. Pediatricians should always consider the possibility of LTP involvement in cases of plant-derived food allergy.

The role of allergoids in allergen immunotherapy: from injective to sublingual route.

Summary: Summary Allergen immunotherapy (AIT) is aimed at inducing tolerance to allergens, such as pollens, dust mites or moulds, by administering increasing amounts of the causative allergen through subcutaneous or sublingual route. The evidence of efficacy of AIT is high, but the issue of safety, especially for the subcutaneous route, must be taken into account. The search for safer AIT products aimed at reducing the allergenicity, and thus adverse reactions, while maintaining the immunogenicity, that is essential for effectiveness, gave rise to the introduction of allergoids, which were conceived to fulfill these requirements. In the first allergoids glutaraldehyde or formaldehyde were used as cross-linking agent to polymerize allergens, this resulting in high molecular weight molecules (200,000 to 20,000,000 daltons) which were significantly less allergenic due to a decreased capacity to bridge IgE on its specific receptor, while maintaining the immunogenicity and thus the therapeutic efficacy. In recent years further agents, acting as adjuvants, such as L-tyrosine, monophosphoryl lipid A, aluminium hydroxide, were added to polymerized extracts. Moreover, a carbamylated monomeric allergoid was developed and, once adsorbed on calcium phosphate matrix, used by subcutaneous route. At the same time, in virtue of its peculiarities, such allergoid revealed particularly suitable for sublingual administration. A lot of clinical evidences show that it is well tolerated, largely safer and effective. Importantly, the higher safety of allergoids allows faster treatment schedules that favor patient compliance and, according to pharmaco-economic studies, they might be more cost-effective than other AIT options.

Omalizumab a new prospective: a nasal polyposis.

Omalizumab, a monoclonal antibody against IgE, may be effective on nasal polyps, but its use is not currently authorized to treat that disease. We report the cases of three patients who were given omalizumab for asthma after undergoing nasal surgical polypectomy. Although such procedure is frequently followed by polyp recurrence, none of the three patients developed this complication, and in one subject the regression of initial polyp return was registered after starting omalizumab. Our data support the hypothesis that omalizumab may be useful to treat nasal polyposis.

New scientific synergies to manage patients with severe Rhinitis: allergy diagnosis and treatment for ENT specialists.

INTRODUCTION: Allergic rhinitis (AR) is a global health problem because of its steadily increasing incidence and prevalence that currently concerns about 30% of the world’s population. Although AR is not a disease that reduces the life expectancy, it is a disorder with a major impact on the quality of life of patients, resulting from an impaired social life, school performance and work productivity. Furthermore, AR produces significant costs for its treatment.

The skin prick test.

The skin prick test (SPT) is the most common test for the diagnosis of allergy. SPT is performed by pricking the skin, usually in the volar surface of the forearm, with a lancet through a drop of an allergen extract and is usually the first choice test in the diagnostic workup for allergic diseases because of its reliability, safety, convenience and low cost. SPT is minimally invasive and has the advantage of testing multiple allergens in 15 to 20 min. In children, SPT is far less disturbing than venipuncture and is used to obtain a sample of serum to measure specific IgE through in vitro tests. There is a good correlation (about 85-95%) between SPT and in vitro tests. Globally, SPT is an excellent diagnostic tool, with a positive predictive value ranging from 95-100%. SPTs can identify sensitivity to inhalants, foods, some drugs, occupational allergens, hymenoptera venom and latex. However, the relevance of such sensitivity to allergens should always be carefully interpreted in the light of the clinical history, because sensitization and clinical allergy may not coincide. In regards to safety, though the reports of systemic reactions, and particularly anaphylaxis, are very rare, in vitro IgE tests should be preferred if previous severe reactions emerge from the patient’s clinical history.

Asthma associated to rhinitis.

A large amount of data show that AR and asthma are associated both epidemiologically and clinically, introducing the definition of “united airway disease”. The mechanisms underlying such association were initially suggested to start from the nose, including the loss of the protective and homeostatic effects of nasal function, the activation of a naso-bronchial reflex and the spread of allergic inflammation from the nose to the lower airways. Later, other factors such as microbial stimuli and systemic inflammatory mechanisms, involving bloodstream and bone marrow, were advocated. The advance in knowledge made it clear that the link between asthma and AR is multifactorial, with particular importance for inflammatory cells and especially eosinophils. By the model of nasal challenge, important immunological responses were revealed, with particular importance for the increased expression of adhesion molecules (ICAM-1, VCAM-1 and E-selectin) and of cytokines such as interleukin (IL)-13, that was accompanied by a rise of eosinophils in blood and developement of bronchial hyper-responsiveness. The occurrence in AR of a concomitant sinusitis is frequently associated with worse asthma outcomes, as assessed by a lower pulmonary function, increased asthma symptoms and poorer quality-of-life compared to patients with asthma alone.

Allergic rhinitis.

Allergic rhinitis (AR) was long considered a quite trivial disease, but the advance in epidemiological and clinical knowledge, with a major role for Allergic rhinitis and its Impact on Asthma (ARIA) initiative, substantially changed the scene. Now we know that AR has significant effects on patients’ quality of life and also has a relevant economic burden. The ARIA phenotypes related to the duration of symptoms and to the severity of AR are very useful in establishing the optimal strategy in each patient with AR, also according to the kind of allergens that cause rhinitis. When traditional allergy testing, including skin prick tests and in vitro of specific IgE antibodies are not sufficient for the diagnosis, modern techniques such as molecular diagnostics may be used. Also the management of AR may be tailored to single patients according to the clinical expression of AR, that may vary from mild to moderate-severe stage, with the aim of achieving the best possible control of the disease.

Is lingual tonsil a preferential target for processing sublingually administered materials?

The oral cavity is a site of pivotal importance in the immune response to foreign antigens, ensuring tolerance induction to harmless agents but reactivity to potentially noxious antigens. Tolerance or reactivity are driven by a number of secondary lymphoid organs, all belonging to the Waldeyer ring, that include adenoids, tubal, palatine and lingual tonsils. Waldeyer's ring tissues were acknowledged as implicated not only in the adaptive immune system but also in the innate immune system modulation, involving the toll-like receptors. In particular, findings from animal studies suggested that the lingual tonsil can be considered as an inductive site sampling and processing antigens to stimulate naïve T and B lymphocytes. According to a recent study showing that immunologically active or inactive materials placed under the tongue of allergic subjects rapidly reach the lingual tonsil, such a role seems likely also in humans, and warrants to be investigated in-depth for possible applications in medical treatments.

Standardization procedure for the nasal nitric oxide measurement method using Niox MINO® and the tidal-breathing technique with velum-closure.

Nitric oxide (NO) is a molecule that performs many functions in the human body. The entire respiratory tract can produce NO, but the highest production occurs in the upper respiratory tract, in the paranasal sinuses in particular. The aim of the present study was to assess a new nasal NO (nNO) measurement method using the Niox MINO Nasal® device (Aerocrine AB, Solna, Sweden) and a special procedure, in order to compare the nNO values obtained in 32 healthy subjects with the values found in the international literature. The measured normal nNO values were equal to 426.76±143.27 ppb, with a 95% confidence interval [160.22-733.30]. Males had an average nNO value equal to 446.76±133.63 [178.64 – 714.02], whereas in females the average value was 403.80±154.90 [94.00-713.60]. This study allows us to confirm that we have been able to establish the normal range of nitric oxide quantity produced in the nasal/sinus cavities of healthy individuals using the Niox MINO Nasal® device and tidal-breathing with velum-closure manoeuvre.

Pre-co-seasonal Allergen Immunotherapy in Parietaria allergic patients.

BACKGROUND: Even though the Parietaria pollen season may be rather long, many physicians think that Parietaria pollen is a perennial allergen present along the whole year. In fact, many doctors prefer to prescribe allergen immunotherapy (AIT) in Parietaria allergic patients, using continuous courses. On the other hand, physicians usually prescribe pre-co-seasonal AIT course for other pollen allergies. OBJECTIVE: This study aimed at investigating whether a single pre-co-seasonal AIT course could be effective in Parietaria allergic patients. METHODS: Globally, 59 subjects (31 males, mean age 35.9 years) were retrospectively evaluated. All were treated with SLIT as a pre-co-seasonal course: 33 with Parietaria extract and 26 with birch extract. Patients' perception of symptom severity and medication use was assessed by visual analogue scale, comparing the previous pollen season and the present. RESULTS: The Parietaria 2012 pollen season started from the 60(th) day and ended at the 205(th) day of 2012. A single pre-co-seasonal SLIT course was able to significantly (p < 0.0001) reduce symptom severity and medication use. CONCLUSION: This preliminary study demonstrates that Parietaria pollen season in Genoa lasted about six months and a single pre-co-seasonal SLIT Parietaria course could be sufficient to reduce symptom severity and medication use.

Prevalence and incidence of reactions to insect stings in children: a reappraisal.

AIM: The prevalence of systemic reactions (SR) to Hymenoptera stings in children was estimated in values lower than 1% in early studies but much higher in recent surveys. We evaluated the current prevalence and the incidence of SR and large local reactions (LLR) to Hymenoptera stings in children in Italy. METHODS: The data on children were collected from the database of the population study on the city of Cotignola, analyzing the answers to the part of the questionnaire about Hymenoptera stings, that concerned if the subject was ever stung by apids or vespids, if there has been a SR or a LLR, and if subjects with reactions received a diagnostic evaluation and a medical treatment. RESULTS: Of the population of 1035 children, 173 (16.7%) were stung at least one time by Hymenoptera. Of them, 5 had had a SR and 9 had had a LLR. This defines a prevalence of SR of 0.5% and of LLR of 0.9%. Only one reaction was severe. Of the 14 subjects with SR or LLR, 5 (35.7%) underwent a diagnostic evaluation and one (7.1%) was treated with venom immunotherapy. The incidence of SR in the subsequent 2 years was 0.09% in the first year and 0.08% in the second year. CONCLUSIONS: These findings do not confirm the recent reports of an increased prevalence of Hymenoptera venom allergy in children. The incidence of SR to stings, thus far unreported for children, was very low both in the first and in the second year.

Evaluation of house dust mite allergy in real life: patients' characteristics and satisfaction with treatment.

BACKGROUND: HDMs are a ubiquitous allergen source, with a very well defined biology, but their role in clinical settings and in everyday clinical practice is not well characterized. Aim of this cross-sectional, questionnaire-based study was to assess the clinical characteristics of HDM-related respiratory allergy in a large population of Italian patients. METHODS: A structured questionnaire was sent to allergists randomly chosen among those of the Italian Federation of Immunology, Allergy and Clinical Immunology (IFIACI). They were asked to fill it with the clinical data of 10-12 consecutive patients referred for respiratory allergy, positive to HDM skin prick test. The questionnaire assessed type and severity of allergy, demographics, yearly distribution of symptoms, treatment, and satisfaction with the therapy. RESULTS: 45 allergists collected data from 499 patients. Within the evaluated population, 42% had rhinitis only, 45% asthma + rhinitis and 13% asthma alone. Rhinitis was moderate/severe in 51% of patients. Asthma was intermittent in 36% of patients, mild in 37% and moderate in 27%. Conjunctivitis was the most frequent comorbidity (36%), followed by rhinosinusitis (16%), adenoid hypertrophy (6%) and polyposis (5%). Out of the population, 56.2% of patients were not at all or partially not satisfied of their treatment for rhinitis, whereas the percentage of dissatisfied patients was about 53% for asthma therapy. 34% patients (n = 170) were monosensitized to HDM. It is confirmed that patients have more symptoms during the fall-winter periods. CONCLUSION: Patients with HDM allergy have frequently moderate-severe rhinitis, and about 50% of them are not satisfied with their treatment.

The evolution of allergen immunotherapy from empirical desensitization to immunological treatment.

In its century-long history, allergen immunotherapy (AIT), has shown continuous evolution in terms of the materials and the treatment schedules used, the adequate duration, and the mechanisms of action underlying its clinical efficacy. The passage from the empirical phase of AIT to the era of evidence-based medicine (EBM) was associated with achievement of the highest levels of evidence. This regarded both forms of AIT currently used, represented by subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). In particular, SLIT tablet preparations of pharmaceutical quality provided physicians and patients a treatment whose efficacy had been confirmed with the highest level of scientific evidence and improved the credibility of AIT for the entire medical field. However, further advances are needed for AIT in terms of optimal patient selection and the required dosage, as well as the quality and composition of the allergen extracts, factors favouring compliance, and the most appropriate duration capable of maintaining the clinical benefit over time.

Towards a global vision of molecular allergology: a map of exposure to airborne molecular allergens.

Allergy diagnostics have changed in the last 10-15 y, moving from the use of extracts for in vivo and in vitro diagnosis to the Component Resolved Diagnosis, based on purified or recombinant allergens. As expected, aerobiology developed similarly, and measurement of allergens in both outdoor and indoor air is now feasible. With the aim of promoting a global view of molecular allergy, we have drawn a map of exposure to molecular aeroallergens in Italy on the bases of geo-climatic regions, maps of pollen distribution, and published data on the molecular profile of sensitization in Italian patients. Given the latitudinal extension of Italy, the profile of exposure to some allergens, such as those of the "Birch Group" and weeds, varies greatly from North to South, while the distribution of exposure to grass allergens is more homogeneous. This map can contribute to a global molecular vision of allergy, helping clinicians to view exposure to pollen in a new way. The exposure profile of the area where patients live can also indicate the correct choice of molecular diagnostics and, therefore, of the appropriate allergen immunotherapy.

Factors influencing the prescription of allergen immunotherapy: the allergen immunotherapy decision analysis (AIDA) study.

The evidence of efficacy of allergen immunotherapy (AIT) for respiratory allergy has been demonstrated by a number of meta-analyses. However, the daily practice of AIT is quite different from controlled trials, facing challenges in terms of selection of patients, practical performance, and, of particular importance, use of allergen extracts of inadequate quality. We here performed a survey, named the Allergen Immunotherapy Decision Analysis (AIDA), to evaluate which criteria are used by specialists to choose a product for sublingual immunotherapy (SLIT) in patients with respiratory allergy. A questionnaire composed of 14 items to be ranked by each participant according to the importance attributed when choosing SLIT products was submitted to 444 Italian specialists. The responses of the 169 (38.1%) physicians, who answered all questions, were analysed. Most of the respondents were allergists (79%), followed by pulmonologists (10.8%), both allergists and pulmonologists (4.8%), and otorhinolaryngologists (3%); 59.8% of the respondents were males and 40.2% were females. The age distribution showed that 89.9% of the respondents were aged between 35 and 64 years. All respondents usually prescribed AIT products in their clinical practice: 31.4% used only SLIT, whereas 69.2% used both subcutaneous and sublingual administration. The rankings, expressed as means, attributed by physicians for each of the 14 items were as follows: level of evidence-based medicine (EBM ) validation of efficacy (3.44), level of EBM validation of safety (4.30), standardization of the product (5.37), efficacy based on personal experience (5.82), defined content(s) of the major allergen(s) in micrograms (5.96), scientific evidence for each single allergen (6.17), safety based on personal experience (6.32), ease of administration protocol (8.08), cost and terms of payment (e.g. instalments) (9.17), dose personalization (9.24), patient preference (9.25), ease of product storage (9.93), reimbursement (10.12), and availability of a helpline or on-line assistance from the manufacturer (11.89). These attitudes need to be taken into consideration by regulatory agencies as well as by producers.

Advances in the quantification of relevant allergens in allergenic extracts.

Relevant allergens are major contributors to the safety and efficacy of allergenic extracts used in allergen immunotherapy (AIT). As such, they should be accurately quantified, as recommended by the 2008 European guidelines on allergen products. Until now, the quantification of relevant allergens was mainly performed by using immunoassays (e.g. ELISA) that relying upon specific antibodies. Although antibody-based quantification is commonly used to assess the concentration of relevant allergens in allergenic extracts, results must be taken with caution in the light of the inherent limitations of such techniques. In the present study, we discuss how those limitations can be overcome by using comprehensive mass spectrometry-based techniques.