Clean labelling sodium nitrite at pilot scale: In-situ reduction of nitrate from plant sources and its effects on the overall quality and safety of restructured cooked ham.

Growing health and environmental concerns have increased demand for all-natural products, with a focus on clean labelling. Sodium nitrite is the most widely used additive in the meat industry because it imparts the typical cured flavour and colour to meat products and, most importantly, their microbiological safety. However, due to health concerns, the European Commission is proposing revised regulations to reduce nitrate and nitrite levels in meat products. As a result, the meat industry is actively seeking alternatives. This study explored the production of four cooked hams utilising nitrate-rich vegetable sources combined with two different nitrate-reducing commercial food cultures, alongside a control ham prepared with sodium nitrite (150 ppm). Microbiological, physico-chemical (pH, water activity, nitrate and nitrite concentration, lipid profile, lipid oxidation) and sensory (texture and colour profile) characterisation of the products was carried out. Challenge tests for Listeria monocytogenes, Clostridium sporogenes and Clostridium perfringens have been performed to assess the growth of pathogens, if present in the products. Results revealed comparable microbiological and physico-chemical profiles across ham formulations, with minor differences observed in colour parameters for sample C. The sensory analysis showed that for the pilot ham formulations A and D, there were no significant differences in consumer perception compared to the control ham. In the challenge tests, L. monocytogenes levels were similar in both control and tested hams. There were no significant differences in C. sporogenes and C. perfringens counts at any temperature or between test and control samples. These results indicate that this technology has a potential future in the cured meat sector, as regulators mandate the reduction of added synthetic chemicals and consumers seek healthier and more natural ingredients in their daily diets.

Anticipating undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry: a decision tool for bronchial challenge testing.

BACKGROUND: Some patients with asthma demonstrate normal spirometry and remain undiagnosed without further testing. OBJECTIVE: To determine clinical predictors of asthma in symptomatic adults with normal spirometry, and to generate a tool to help clinicians decide who should undergo bronchial challenge testing (BCT). METHODS: Using random-digit dialling and population-based case-finding, we recruited adults from the community with respiratory symptoms and no previous history of diagnosed lung disease. Participants with normal pre- and post-bronchodilator spirometry subsequently underwent BCT. Asthma was diagnosed in those with symptoms and a methacholine provocative concentration (PC20) of < 8 mg/ml. Sputum and blood eosinophils, and exhaled nitric oxide were measured. Univariate analyses identified potentially predictive variables, which were then used to construct a multivariable logistic regression model to predict asthma. Model sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated. RESULTS: Of 132 symptomatic individuals with normal spirometry, 34 (26%) had asthma. Of those ultimately diagnosed with asthma, 33 (97%) answered 'yes' to a question asking whether they experienced cough, chest tightness or wheezing provoked by exercise or cold air. Other univariate predictors of asthma included female sex, pre-bronchodilator FEV1 percentage predicted, and percent positive change in FEV1 post bronchodilator. A multivariable model containing these predictive variables yielded an AUC of 0.82 (95% CI: 0.72-0.91), a sensitivity of 82%, and a specificity of 66%. The model was used to construct a nomogram to advise clinicians which patients should be prioritized for BCT. CONCLUSIONS: Four readily available patient characteristics demonstrated a high sensitivity and AUC for predicting undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry. These characteristics can potentially help clinicians to decide which individuals with normal spirometry should be investigated with bronchial challenge testing. However, further prospective validation of our decision tool is required.

The Use of Exercise Challenge Testing and Fractional Exhaled Nitric Oxide in Diagnosis of Chest Tightness Variant Asthma in Children.

BACKGROUND: Chest tightness variant asthma (CTVA) in children presents with chest tightness as the sole manifestation. Diagnostic tests are needed given the lack of typical asthma symptoms. The present study aimed to investigate the diagnostic value of exercise challenge testing (ECT) and fractional exhaled nitric oxide (FeNO) in pediatric CTVA. METHODS: We included 98 children aged 6-13 years with chest tightness as the sole symptom for >4 weeks. All subjects underwent FeNO measurement, spirometry and ECT, and received 4-week budesonide/formoterol treatment. According to treatment responses, children were categorized into CTVA (n = 12) and non-CTVA (n = 86) groups. Differences in clinical characteristics and FeNO, spirometry, and ECT results were compared between the two groups. The FeNO and ECT diagnostic performances were determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Children with CTVA exhibited significantly higher Mycoplasma pneumoniae IgG, total IgE, and FeNO values; greater post-ECT forced expiratory volume in 1 s (FEV1) fall; and more frequent sensitization to mites and pets than those without CTVA. Further logistic regression revealed that higher FEV1 fall (OR, 1.39; 95% CI: 1.11-1.74; p = 0.004) and higher FeNO values (OR, 1.04; 95% CI: 1.01-1.08; p = 0.014) were risk factors associated with CTVA. FEV1 fall and FeNO had similar areas under the ROC curve (AUCs) (0.79 vs. 0.78; p = 0.924), and their optimal CTVA-prediction cutoff values were 9.9% and 15.0 ppb, respectively. The AUC of FEV1 fall and FeNO combination was higher at 0.86 (95% CI: 0.78-0.93); however, no difference was observed using the single test (p > 0.05). Their combination exhibited a relatively higher sensitivity than that of FEV1 fall alone (0.75 vs. 0.67) and higher positive predictive value than that of FeNO alone (0.60 vs. 0.29). CONCLUSION: CTVA is a cause of unexplained recurrent chest tightness in children. FeNO ≥15.0 ppb and post-ECT FEV1 fall ≥9.9% are diagnostically valuable for CTVA in children, with their combination potentially contributing to greater diagnostic accuracy.

Baseline Spirometry as a Predictor of Positive Methacholine Challenge Testing for Exertional Dyspnea.

BACKGROUND: There are several tests recommended by the American Thoracic Society (ATS) to evaluate for airway hyper-responsiveness (AHR), one of which is methacholine challenge testing (MCT). Few studies have examined the correlation of baseline spirometry to predict AHR in MCT, especially in the younger, relatively healthy military population under clinical evaluation for symptoms of exertional dyspnea. The study aim was to retrospectively correlate baseline spirometry values with MCT responsiveness. METHODS: This study is a retrospective review of all MCT performed at Brooke Army Medical Center/Wilford Hall Medical Center over a 12-y period; all completed studies were obtained from electronic databases. The following parameters were analyzed from the studies: baseline FEV1, FVC, FEV1/FVC, mid-expiratory flow (FEV25-75%), FEV25-75%/FVC. Studies were categorized based on baseline obstruction, restriction, FEF25-75% lower limit of normal, and response to bronchodilator testing (if completed); these values were compared based on methacholine reactivity and severity. RESULTS: Methacholine challenge studies (n = 1,933) were reviewed and categorized into reactive (n = 577) and nonreactive (n = 1,356) as determined by ATS guidelines. The mean baseline FEV1 (% predicted) with MCT reactivity was 88.0 ± 13.0% versus no MCT reactivity was 92.7 ± 13.0% (P < .001). The mean baseline FVC (% predicted) was 93.1 ± 13.7% versus 95.3 ± 13.5% (P < .001). The mean baseline FEV25-75% (% predicted) was 80.0 ± 22.1% versus 89.0 ± 23.4% (P < .001). Based on partition analysis, methacholine reactivity was most prevalent with baseline obstruction, n = 115 (43%), and in the absence of obstruction, when the FEF25-75% (% predicted) was below 0.70, n = 111 (40%). The negative predictive value with normal spirometry was 73%. CONCLUSIONS: The analysis of baseline spirometry prior to MCT proved useful in the evaluation of exertional dyspnea in a military population. The presence of airways obstruction (FEV1/FVC < lower limit of the normal range) followed by a reduction in FEV25-75% < 70% predicted showed a positive correlation with underlying AHR. In patients with exertional dyspnea and normal baseline spirometry, the use of the FEF25-75% may be a useful surrogate measurement to predict reactivity during MCT and consideration for additional testing or treatment.

Predictors of methacholine challenge testing results in subjects without airflow obstruction.

OBJECTIVE: Methacholine challenge testing (MCT) is considered when asthma remains clinically suspected despite normal spirometry. Few studies have attempted to determine the predictive factors of MCT results. We aimed to establish which demographic data, clinical symptoms, pulmonary function testing results, and laboratory values were associated with abnormal MCT (provocation concentration causing a 20% decrease in FEV1 (PC20) ≤ 16 mg/mL) in subjects without airflow obstruction on spirometry. METHODS: All patients who completed MCT at Montfort Hospital between January 1st, 2016 and December 31st, 2018 were identified. Subjects with a reduced FEV1/FVC ratio were excluded. We used Pearson's chi-squared test and point-biserial correlation method to determine which variables had a significant relationship (p < 0.05) with MCT results. RESULTS: 23.3% of patients who underwent MCT had airflow limitation. In the 1126 subjects with a normal FEV1/FVC ratio, PC20 ≤ 16 mg/mL was found in 13.0%. Younger age, female gender, body mass index ≥ 40, and reported wheezing were factors associated with increased probability of airway hyper responsiveness. Lower FEV1, significant improvement of the FEV1 post-bronchodilator, reduced FEF25%-75%, greater FEF25%-75% reversibility, airway resistance measurements above the upper limit of normal, and increased blood eosinophil counts were predictive of abnormal MCT. CONCLUSIONS: Only 13.0% of patients referred for MCT had a PC20 ≤ 16 mg/mL when the FEV1/FVC ratio was normal, highlighting the need to further define in which individuals this test is truly warranted. Further investigation is required to develop an easy-to-use and validated prediction model in order to better understand patients' pretest probability of abnormal MCT.

Utility and efficiency of methacholine challenge testing in evaluating pediatric asthma: unraveling the diagnostic conundrum.

OBJECTIVE: Interpretation of methacholine challenge testing (MCT) results depends on the patient's pretest probability of asthma as well as the provocative concentration (PC20); however, ordering providers rarely understand the complexity associated with its interpretation. This study investigated the clinical utility and efficiency of MCT at a tertiary center in evaluating pediatric asthma. METHODS: Retrospective chart review was done for all MCT done at a tertiary center over a six year period (2011-2017). Demographics, referring provider, referral diagnosis, current symptoms with and without exercise, and baseline spirometry were collected. Pretest probability of asthma was assigned by author (RB) who was blinded to MCT results and PC20. Post-test probability of asthma was assigned based on pretest probability, MCT result (+/-), and PC20. Three assigned asthma probability categories were "unlikely" "likely", and "very likely". RESULTS: Of 172 subjects (91 Females, age range 5-21 years), 64.9% of MCT results (n = 111)) were negative and 35.1% (n = 60)) were positive. One was inconclusive. Those who tested positive were shorter, lighter, younger and had lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio than those who tested negative (p < 0.05). Subjects with exercise symptoms only were less likely to test positive (OR 0.2, CI 0.1-0.5). In a majority of subjects (91.8%; 157/171), MCT increased the certainty of presence or absence of asthma. CONCLUSIONS: In our subject population, MCT could be useful in evaluating pediatric asthma if subject's pretest probability of asthma and PC20 was taken into account. It was not as useful for subjects with exercise symptoms only.

Estimating Listeria monocytogenes Growth in Ready-to-Eat Chicken Salad Using a Challenge Test for Quantitative Microbial Risk Assessment.

Currently, there is a growing preference for convenience food products, such as ready-to-eat (RTE) foods, associated with long refrigerated shelf-lives, not requiring a heat treatment prior to consumption. Because Listeria monocytogenes is able to grow at refrigeration temperatures, inconsistent temperatures during production, distribution, and at consumer's household may allow for the pathogen to thrive, reaching unsafe limits. L. monocytogenes is the causative agent of listeriosis, a rare but severe human illness, with high fatality rates, transmitted almost exclusively by food consumption. With the aim of assessing the quantitative microbial risk of L. monocytogenes in RTE chicken salads, a challenge test was performed. Salads were inoculated with a three-strain mixture of cold-adapted L. monocytogenes and stored at 4, 12, and 16 °C for eight days. Results revealed that the salad was able to support L. monocytogenes' growth, even at refrigeration temperatures. The Baranyi primary model was fitted to microbiological data to estimate the pathogen's growth kinetic parameters. Temperature effect on the maximum specific growth rate (µmax ) was modeled using a square-root-type model. Storage temperature significantly influenced µmax of L. monocytogenes (p < 0.05). These predicted growth models for L. monocytogenes were subsequently used to develop a quantitative microbial risk assessment, estimating a median number of 0.00008726 listeriosis cases per year linked to the consumption of these RTE salads. Sensitivity analysis considering different time-temperature scenarios indicated a very low median risk per portion (<-7 log), even if the assessed RTE chicken salad was kept in abuse storage conditions.

The utility of drug challenge testing in Brugada syndrome: A systematic review and meta-analysis.

INTRODUCTION: Brugada syndrome (BrS) is associated with ventricular arrhythmia leading to sudden cardiac death. Risk stratification is challenging, as major arrhythmic events (MAEs) are rare. We assessed the utility of drug challenge testing in BrS by a systematic review and meta-analysis. METHODS AND RESULTS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies compared the incidence of MAE between spontaneous and drug challenge-induced Type 1. Mixed-effects Poisson regression was used to calculate the incidence rate ratio (IRR). Eighteen studies from 2006 to 2018 were included (4099 patients, mean follow-up: 4.5 years). Pooled annual incidences of MAE in spontaneous, drug challenge induced (regardless of symptoms), asymptomatic drug challenge induced, and symptomatic drug challenge-induced Type 1 were 23.8 (95% confidence interval [CI]: 19.8-27.8), 6.5 (95% CI: 3.9-9.1), 2.1 (95% CI: -0.3 to 4.4), and 19.6 (95% CI: 9.9-29.3) per 1000 person-years, respectively. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was not statistically different (IRR = 1.0; 95% CI: 0.6-1.7). CONCLUSIONS: The incidence of MAE in drug challenge-induced Type 1 in asymptomatic patients is low. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was similar.

Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis.

BACKGROUND: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). RESEARCH QUESTION: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. STUDY DESIGN AND METHODS: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. RESULTS: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. INTERPRETATION: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

Microbiological Stability and Overall Quality of Ready-To-Heat Meals Based on Traditional Recipes of the Basilicata Region.

The quality of ready meals is affected by several factors that may impair stability and nutritional value. In this work, we evaluated the overall quality of four traditional meals (Basilicata region) prepared according to the cook&chill method, packaged in air or modified atmosphere packaging (MAP; 70% N2 and 30% CO2), and stored at 4 °C for seven days. The shelf-life was determined by Listeria monocytogenes challenge testing and inactivation by microwave (MW) heating was assessed. The counts at the production day were excellent in three meals out of four, whereas one had high levels of spoilage and pathogens both as soon as the preparation and after seven days. MAP was partially effective only against the growth of the aerobic mesophilic species, whereas sensory analysis revealed that MAP may preserve many of sensory attributes. The average shelf-life of the meals ranged from 11 to 13 days, however, the potential shelf-life was undetectable in one out four meals, as L. monocytogenes growth was inhibited two days after the inoculum. In the inoculated meals, MW heating provided a partial inactivation (25%) of the pathogen. The overall quality of type the meals was partially satisfactory; post-cooking contaminations may affect the microbial load and reduce the palatability over the storage period and, above all, may involve biological hazards which consumers' habits may not be able to eliminate.

Assessment of portable oxygen concentrators in infants undergoing hypoxic challenge testing. A randomised controlled crossover trial.

AIM: Due to reduced PaO2 , aircrafts at cruising altitudes are pressurised to a cabin altitude of 2438 m, equivalent to breathing FiO2 0.15. Portable oxygen concentrators (POCs) are approved for onboard oxygen supply with lack of evidence, especially in infants. We assessed POCs (continuous-flow cPOC vs. pulsed-flow pPOC) under simulated altitude conditions performing Hypoxic Challenge Testing (HCT). METHODS: In a randomised controlled crossover trial, we included patients <1 year born prematurely. In incidents of hypoxia (SpO2  ≤ 85%), oxygen was administered through POC. In patients with a positive hypoxia reversal, HCT was repeated 24 hours later. If hypoxia occurred during the second testing, oxygen was given using the alternative POC. RESULTS: We randomised 26 patients; 22 patients received allocated intervention (4 dropped out). Mean gestational age 30.4 weeks, mean corrected age 38.2 weeks. Both POCs achieved immediate hypoxia reversal in all cases (SpO2 cPOC/pPOC 98%/99.4% (95%CI -2.91, 0.01)) without any adverse events. No significant difference was observed in patients with BPD. CONCLUSION: Both POCs generated sufficient oxygen to reverse HCT induced hypoxia. Although pPOCs are not recommended in paediatric age, our data suggest their effectiveness even in neonates without any associated adverse events. Future research on pPOCs safety is required to establish recommendations for their use.

Exhaled nitric oxide can't replace the methacholine challenge in suspected pediatric asthma.

BACKGROUND: In adults, measurement of FENO has been recently suggested as a substitute for the methacholine challenge test (MCT) for diagnosis of asthma. This study aimed to evaluate whether FeNO is a substitute for MCH also in children with suspicious asthma. METHODS: During a single visit steroid naive children (5-17 years) with suspicious asthma underwent skin prick test (SPT), FENO measurement and spirometry prior and during MCT (one concentration procedure). Results of the SPT (atopy/non-atopy) and MCT (asthma/non-asthma) were used for categorization. ROC analysis in atopy non-atopy subgroups yielded sensitivity, specificity, positive and negative predictive value (PPV and NPV) for FENO. RESULTS: The SPT revealed atopy in 134 out of 222 children (age 9.7 ±â€¯3.2 years) investigated and asthma was diagnosed in 114 (77/37 atopy/non-atopy) patients. FENO values in patients with atopic asthma were significantly higher compared to those with either non-atopic asthma or atopia without asthma (18 ppb (5-89) vs 7 ppb (5-36); p < 0.001; 18 ppb (5-89) vs 11 ppb (5-98); p < 0.05). Sensitivity and specificity of FENO for diagnosing atopic asthma (FENO≥15.5 ppb; AUC = 0.635, p < 0.01) were 61.1% and 64.9% and non-atopic asthma (FENO≥ 6.5 ppb; AUC = 0.445, p = 0.382) 54.1% and 39.2%, respectively. The PPV/NPV for FENO were 0.70/0.55 in atopy and 0.39/0.54 in non-atopy patients, respectively. CONCLUSION: In children, FENO is not appropriate to substitute for the MCT. However, in patients with a negative SPT a FENO in the normal range makes the presence of atopic asthma unlikely.

Short-term effect of once-daily fluticasone furoate on methacholine-induced bronchoconstriction in mild asthmatics.

BACKGROUND: Inhaled corticosteroids (ICS) decrease airway inflammation and airway hyperresponsiveness (AHR). Previous studies have generally investigated the effect of ICS on methacholine-induced AHR following weeks or months of medium to high dose treatment. PURPOSE: The short-term effects of once-daily fluticasone furoate (FF) 100 mcg on methacholine-induced AHR and airway inflammation were examined over the course of one week. METHODS: Eleven mild asthmatics completed this randomized, double-blind crossover study. Once-daily FF (100 mcg) and identical appearing placebo Ellipta® inhalers were given for 7 days with a 2-week washout. Methacholine challenges were performed before and 24 h after the first, third and seventh doses. Fractional exhaled nitric oxide (FeNO) was measured initially and at 7 days. RESULTS: FF significantly (p = 0.0009-0.0078) increased methacholine PD20 (provocative dose causing 20% fall in forced expiratory volume in 1 s) at all times. Doubling dose shifts (95% CI) were 1.23 (0.60-1.86), 1.17 (0.68-1.67) and 1.44 (0.93-1.94) after the first, third and seventh dose respectively. FeNO (geometric mean, 95% CI) decreased significantly (p = 0.0049) following FF treatment from 37.9 ppb (23.7-60.5) initially to 22.9 ppb (14.8-35.5) at 7 days. Placebo did not affect methacholine PD20 or FeNO. CONCLUSION: Single-dose FF 100 mcg decreased methacholine AHR at 24 h without significant further improvement with continued daily use over 7 days. The inhibition in AHR after one week of daily dosing coincided with a significant decrease in FeNO at 7 days. Contrary to past assumptions, the ICS FF appears to rapidly reduce AHR to methacholine.

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status.

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.

Differential diagnosis of late-type reactions to injected local anaesthetics: Inflammation at the injection site is the only indicator of allergic hypersensitivity.

BACKGROUND: Anaphylaxis-like reactions developing within a few minutes are the most frequent complications of subcutaneous or submucosal injections of local anaesthetics (LAs), and topically applied LAs are potential contact allergens. In addition, injected LAs have been reported to induce delayed reactions, including local inflammation at the injection site, and various general symptoms. OBJECTIVES: To assess the frequency and symptoms of late-type hypersensitivity occurring several hours after LA injections. METHODS: We retrospectively evaluated clinical data and test results from all patients referred to our allergy clinic in a period of 20 years for diagnostic work-up of LA-associated late-type reactions. RESULTS: Of 202 patients reporting symptoms with onset at least 1 hour after LA injection, 40 had cutaneous inflammation confined to the injection site, and 162 reported various systemic symptoms. LA hypersensitivity could be excluded in all patients with systemic complaints by means of skin testing and subsequent subcutaneous provocation. In 8 of the 40 patients (20%) with local inflammatory reactions, late-type allergic LA hypersensitivity was confirmed. CONCLUSIONS: Late-type LA allergy commonly causes inflammatory skin reactions confined to the injection site. Conversely, LAs are highly unlikely to trigger delayed systemic symptoms such as urticarial or exanthematous skin eruptions.

Dose omission to shorten methacholine challenge testing: clinical consequences of the use of a 10% fall in FEV1 threshold.

INTRODUCTION: In methacholine challenge testing (MCT), skipping a methacholine dose is suggested if FEV1 falls by < 5%. Using a larger threshold may further shorten test duration, but data supporting this hypothesis is lacking. We evaluated the safety and consequences of using a 10% FEV1 fall as threshold to skip the next dose of methacholine in patients undergoing MCT. METHODS: We reviewed MCTs performed in our center in 2017-2018. A ≤ 10% FEV1 fall allowed the omission of the next methacholine dose. Patients of interest were those in which a dose was skipped after a previous FEV1 fall outside the usual range (5-10%, termed "skip5-10%"). Adverse events [AE; mild: > 1 nebulized salbutamol dose (2.5 mg) to reach basal FEV1, palpitations; severe: hypoxemia and/or need for medical attention or intervention] were compared in the skip5-10% group and others. Regression analysis was used to identify predictors of AE. RESULTS: 208 MCTs were analysed (135 males, age 52 ± 15 years). Skip5-10% occurred 111 times in 90 tests. Prevalence of AE was 5% and all were mild. Patients who developed AEs had lower FEV1, FVC and FEV1/FVC ratio, and higher lung volume values (all p < 0.05), but similar prevalence of skip5-10% (36 vs. 44%, p = 0.64). Overall, MCTs in which at least one skip5-10% occurred had a lower mean number of doses (3.1 ± 0.6 vs. 3.5 ± 1.3 doses, p = 0.007). Baseline residual volume was independently related to the development of AEs (OR 1.05, 95% CI 1.01-1.10, p = 0.01), but not the presence of a skip5-10%, even when the skipped dose directly led to the reaching of PC20 (OR 5.40, 95% CI 0.73-39.22, p = 0.10). CONCLUSION: Omitting a methacholine dose based on a ≤ 10% fall in FEV1 occurs frequently and has the potential to shorten test duration. AE are rare, but patients with worse baseline lung function and gas trapping are at increased risk of mild side effects.

Twenty Years' Experience with Anaphylaxis-Like Reactions to Local Anesthetics: Genuine Allergy is Rare.

BACKGROUND: Anaphylaxis-like reactions occur within minutes after the application of local anesthetics (LA), most commonly during dental interventions. Impressive symptoms including respiratory distress or loss of consciousness frequently give rise to a suspicion of allergy and may prompt patients and treating physicians to refuse future LA injections. OBJECTIVE: Nonallergic mechanisms are responsible for the majority of LA-induced immediate-type reactions. In view of the preponderance of nonallergic reactions, the question arises whether genuine LA allergy may be missed during routine testing procedures. METHODS: We retrospectively evaluated clinical data and test results from patients referred to our allergy clinic within the past 20 years for diagnostic workup of LA-induced immediate-type reactions. RESULTS: Of 402 evaluated patients, 29 had an episode of acute urticaria within 30 minutes after LA injections, and the remaining 373 had a history of mainly subjective cutaneous, respiratory, cardiovascular, and neurological complaints. Of the patients reporting urticaria with or without angioedema, 14 were diagnosed with a spontaneous episode of urticaria, 13 had allergic or nonallergic reactions to other agents, and 2 had IgE-mediated LA allergy. LA allergy was definitely excluded by 771 subcutaneous provocation tests with skin test negative LA, thereby demonstrating the high predictive value of negative intradermal testing. CONCLUSIONS: Skin testing and provocative LA challenge are useful to exclude LA allergy, and this testing procedure seems to be appropriate to identify the extremely rare cases with IgE-mediated LA allergy.

Patterns of bronchial challenge testing in Canada.

BACKGROUND: Bronchial challenge testing (BCT) measures airway hyperresponsiveness; asthma guidelines recommend using BCT when symptoms manifest despite normal spirometry. Improper application of these guidelines commonly results in the misdiagnosis of asthma. Yet, statistics concerning BCT remain largely obscure. The current paper addresses this gap and explores how various health variables may elucidate adherence to asthma guidelines and patterns of BCT across Canadian provinces. METHODS: Using the Access to Information Act, medical financial claims for BCT (or equivalent procedures) were requested from each of the Canadian provinces and territories. Based on the available information (from provinces only), correlations between frequency of BCT claims and medical demographics (e.g., prevalence of respirologists, health expenditures) are reported. RESULTS: Controlling for population or for people with asthma, physicians from Québec claim four times more BCT per year than those in other provinces; physicians from Alberta close to eight-fold fewer. The number of respirologists per capita and BCT per capita correlated moderately, r(132) = 0.582, p < 0.001, [95% CI 0.421, 0.716]. Excluding "outliers" (i.e., British Columbia, Alberta, and Saskatchewan) greatly strengthened this correlation, r(87) = 0.930, p < 0.001, [95% CI 0.883, 0.958]. DISCUSSION: These findings demonstrate that provinces vary in their use of BCT. This result seems to stem, at least in part, from differences in the prevalence of respirologists. Interestingly, geographic region appears to wield a strong influence; in the correlation between number of tests and number of respirologists, physicians from Western provinces (i.e., Alberta, Saskatchewan, and British Columbia) administered fewer tests than their Eastern colleagues. Given the association between inadequate application of BCT and misdiagnosis of asthma, physicians should pay special attention to the Canadian guidelines when considering an asthma diagnosis.

Methacholine Challenge: Comparison of Airway Responsiveness Produced by a Vibrating Mesh Nebulizer Versus a Jet Nebulizer.

BACKGROUND: The latest methacholine challenge testing (MCT) guidelines published by the European Respiratory Society recommend the characterization of nebulizers before their use in clinics and research. Such investigations are necessary for accurately determining the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) delivered by a given device. The standard English Wright (Wright) jet nebulizer recommended in the 1999 guidelines by the American Thoracic Society has become difficult to obtain and possesses some characteristics that complicate the calculation of dose delivery from this device (e.g. evaporation). Our objective was to determine if the Aerogen® Solo (Solo) vibrating mesh nebulizer provides similar methacholine challenge test results compared to the currently used Wright jet nebulizer. METHODS: Sixty mild-to-moderate asthmatics were studied across three research sites in a randomized crossover study. Both methacholine challenges were completed at least 24 hours apart within a 2-week period. Testing with the Wright device was performed as per the 2-minute tidal breathing protocol. The Solo study arm followed the same procedure except for a shorter inhalation time of 1 minute. The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) and the methacholine PD20 were calculated following each methacholine challenge. RESULTS: The geometric mean methacholine PC20 values for the Solo and the Wright differed statistically (0.65 mg/mL vs. 2.58 mg/mL, respectively, p < 0.00001) and clinically. Between-nebulizer geometric mean methacholine PD20 results are comparable by clinical standards [81.7 µg (Solo) vs. 64.7 µg (Wright)], although the slight difference in dose was statistically significant (p = 0.018). CONCLUSIONS: The comparability of PD20 values between the Solo and the Wright validates the importance of reporting airway responsiveness to methacholine in terms of dose and not concentration, as stressed in the latest testing guidelines. This finding along with several benefits associated with the Solo make it a promising nebulizer for performing MCT.