Drop In Forced Expiratory Volume Research Articles

Bronchoalveolar lavage cytokine-based risk stratification of minimal acute rejection in clinically stable lung transplant recipients

Acute cellular rejection (ACR) remains the most significant risk factor for chronic lung allograft dysfunction (CLAD). While clinically significant or higher-grade (≥A2) ACR is generally treated with augmented immunosuppression (IS), the management of clinically stable grade A1 ACR remains controversial. At our center, patients with clinically stable grade A1 ACR are routinely not treated with augmented IS. While the overall outcomes in this group of patients at our center are equivalent to patients with stable A0 pathology, CLAD and death rates remain overall high. We hypothesized that a distinct cytokine signature at the time of early minimal rejection state would be associated with worse outcomes. Specifically, we aimed to determine whether bronchoalveolar lavage (BAL) biomarkers at the time of first clinically stable grade A1 ACR (CSA1R) are predictive of subsequent CLAD or death. Among all adult, bilateral, first lung transplants, performed 2010-2016, transbronchial biopsies obtained within the first-year post-transplant were categorized as clinically stable or unstable based on the presence or absence of ≥10% concurrent drop in forced expiratory volume in 1 second (FEV1). We assessed BAL samples obtained at the time of CSA1R episodes, which were not preceded by another ACR (i.e., first episodes). Twenty-one proteins previously associated with ACR or CLAD were measured in the BAL using a multiplex bead assay. Association between protein levels and subsequent CLAD or death was assessed using Cox Proportional Hazards models, adjusted for relevant peri-transplant clinical covariates. We identified 75 patients with first CSA1R occurring at a median time of 98 days (range 48.5-197) post-transplant. Median time from transplant to CLAD or death was 1247 (756.5-1921.5) and 1641 days (1024.5-2326.5), respectively. In multivariable models, levels of MCP1/CCL2, S100A8, IL10, TNF-receptor 1, and pentraxin 3 (PTX3) were associated with both CLAD development and death (p < 0.05 for all). PTX3 remained significantly associated with both CLAD and death after adjusting for multiple comparisons. Our data indicate that a focused BAL protein signature, with PTX3 having the strongest association, may be useful in determining a subset of CSA1R patients at increased risk and may benefit from a more aggressive management strategy.

Regional airflow obstruction after bronchoconstriction and subsequent bronchodilation in subjects without pulmonary disease.

Some subjects with asthma have ventilation defects that are resistant to bronchodilator therapy, and it is thought that these resistant defects may be due to ongoing inflammation or chronic airway remodeling. However, it is unclear whether regional obstruction due to bronchospasm alone persists after bronchodilator therapy. To investigate this, six young, healthy subjects, in whom inflammation and remodeling were assumed to be absent, were bronchoconstricted with a PC20 [the concentration of methacholine that elicits a 20% drop in forced expiratory volume in 1 s (FEV1)] dose of methacholine and subsequently bronchodilated with a standard dose of albuterol on three separate occasions. Specific ventilation imaging, a proton MRI technique, was used to spatially map specific ventilation across 80% of each subject's right lung in each condition. The ratio between regional specific ventilation at baseline and after intervention was used to classify areas that had constricted. After albuterol rescue from methacholine bronchoconstriction, 12% (SD 9) of the lung was classified as constricted. Of the 12% of lung units that were classified as constricted after albuterol, approximately half [7% (SD 7)] had constricted after methacholine and failed to recover, whereas half [6% (SD 4)] had remained open after methacholine but became constricted after albuterol. The incomplete regional recovery was not reflected in the subjects' FEV1 measurements, which did not decrease from baseline (P = 0.97), nor was it detectable as an increase in specific ventilation heterogeneity (P = 0.78).NEW & NOTEWORTHY In normal subjects bronchoconstricted with methacholine and subsequently treated with albuterol, not all regions of the healthy lung returned to their prebronchoconstricted specific ventilation after albuterol, despite full recovery of integrative lung indexes (forced expiratory volume in 1 s and specific ventilation heterogeneity). The regions that remained bronchoconstricted following albuterol were those with the highest specific ventilation at baseline, which suggests that they may have received the highest methacholine dose.

Observation of the Improvement in Nocturnal Asthma Symptoms with Administration of Once Daily Sustained Released Theophylline

Objective: The aims and objective of this study to observe the improvement in Nocturnal Asthma symptoms and Quality of Life (QoL) with administration of once daily sustained release theophylline preparation.Background: Nocturnal symptoms are a common part of the asthma. Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV1) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma, which may include improvement in QoL.Methodology: The patient with Chronic Persistent Asthma, both sex, age &gt;18 to 50 years of age and preferably patients with nocturnal exacerbations were included in the study. All patients were diagnosed on the basis of clinical history, physical examination, chest X-ray and pulmonary function tests, in accordance with the clinical criteria for the diagnosis by the GINA. The recruitment period was between March 2017 and August 2017 Shaheed Suhrawardy Medical College Hospital, Dhaka.Results: It was observed that 65(92.85%) was found exacerbation free night and 5(7.15%) patients were found exacerbation with sustained release Theophylline. There are significantly improved qualities of life between 1st follow up to 2nd follow up, 3rd follow up and 4th follow up p&lt;0.001 which was statistically significant. Spirometry test was gradually improved between 1st visit of FEV1 to 2nd, 3rd and 4th visit of FEV1, (p&lt;0.001) that was statistically significant.Conclusion: Most of the patients were found exacerbation free night. There are significantly improved quality of life between 1st follow up to 2nd follow up, 3rd follow up and 4th follow up in Spirometry test. The value of FEV1 was gradually improve in the lst visit, 2nd, 3rd and 4th visit with sustained release Theophylline.J Shaheed Suhrawardy Med Coll, December 2017, Vol.9(2); 74-77

FeNO and Exercise Testing in Children at Risk of Asthma

Exercise testing is the gold standard for diagnosing exercise-induced bronchoconstriction in children, but requires considerable cooperation and medical resources. Therefore, fraction of exhaled nitric oxide (FeNO) has been proposed as a tool to predict the need for exercise testing. The objective of this study was to investigate the relationship between FeNO, exercise test results, and a history of respiratory symptoms during exercise in children at risk of asthma. FeNO measurement, exercise testing, and interview about respiratory symptoms during exercise were completed in 224 seven-year-old children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood2000 birth cohort. The associations between FeNO, exercise test results, and reported respiratory symptoms during exercise were analyzed adjusting for gender, respiratory infections, and inhaled corticosteroid treatment. The associations were also analyzed stratified by asthma and atopic status. Of the 224 children, 28 (13%) had an established asthma diagnosis and 58 (26%) had a positive exercise test (≥15% drop in forced expiratory volume in 1 second [FEV1] from baseline). FeNO and bronchial obstruction after exercise were linearly associated with a doubling of FeNO corresponding to a 2.4% drop in FEV1 (95% confidence interval, 0.8-4.1; P<.01). However, a receiver operating characteristic curve analysis showed that the best cutoff of FeNO for predicting exercise test outcome among children who reported respiratory symptoms during exercise was 17 ppb, which only had 74% negative predictive value. There was no association between FeNO and reported respiratory symptoms during exercise (odds ratio= 1.3 [0.8-1.9]; P= .29) or reported symptoms during exercise and exercise test results (odds ratio= 1.0 [1.0-1.1]; P= .12). A history of respiratory symptoms during exercise was not associated with either elevated FeNO or a positive exercise test in children at risk of asthma. FeNO and exercise test results were linearly associated traits, but FeNO could not reliably be used dichotomized to predict the need of exercise testing.

Small airway involvement in the late allergic response in asthma.

Allergy and asthma are closely linked. Inhalation of allergen induces an early allergic response (EAR) within the airways of allergic asthmatic subjects, which is followed by a late allergic response (LAR) in approximately 50% of the subjects. The LAR is defined as a drop in forced expiratory volume in 1 second (FEV1 ) from baseline usually occurring 4-8 hours after exposure and is believed to affect small airways. However, FEV1 is insensitive to changes in small airway physiology. Our aim was to investigate and compare the pathophysiological processes in large and small airways during the EAR and the LAR and to characterize subjects with both an EAR and a LAR (dual responders) versus those with an EAR only (single responders). Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Lung physiology was assessed by spirometry, impulse oscillometry (IOS), body plethysmography, inert gas washout, single breath methane dilution carbon monoxide diffusion and exhaled breath temperature (EBT), at baseline and repeatedly for 23 hours post-allergen challenge. Peripheral airway resistance, air trapping and ventilation heterogeneity were significantly increased in dual responders (n = 15) compared to single responders (n = 19) 6-8 hours post-challenge. Parameters of peripheral airway resistance and ventilation heterogeneity, measured with IOS and inert gas washout, respectively, correlated at baseline and during the allergic airway response in all subjects. The LAR involves increased resistance and ventilation defects within the peripheral airways. Alternative definitions of the LAR including small airways pathophysiology could be considered. Small airway dysfunction during the LAR suggests that dual responders may have more extensive airway pathology and underscores the relevance of small airways assessment in asthma.

Drop in lung function during asthma and COPD exacerbations - can it be assessed without spirometry?

BackgroundWhen assessing patients with exacerbation of asthma or COPD, it may be useful to know the drop in forced expiratory volume in 1 second (FEV1) compared with stable state, in particular when considering treatment with oral corticosteroids. The objective of the study was to identify indicators of drop in FEV1 during exacerbations.MethodsIn this prospective multicenter study from primary care, patients diagnosed with asthma or COPD were examined at stable state and during exacerbations the following year. Symptoms, chest findings, and pulse oximetry were recorded, and spirometry was performed. A fixed drop in FEV1 (10% and ≥200 mL) and percentage change in FEV1 were outcomes when possible indicators were evaluated.ResultsThree hundred and eighty patients attended baseline examination, and 88 with a subsequent exacerbation were included in the analysis. Thirty (34%) had a significant drop in FEV1 (10% and 200 mL). Increased wheezing was the only symptom associated with this drop with a likelihood ratio of 6.4 (95% confidence interval, 1.9–21.7). Crackles and any new auscultation finding were also associated with a significant drop in FEV1, as was a ≥2% drop in oxygen saturation (SpO2) to ≤92% in the subgroup diagnosed with COPD. Very bothersome wheezing and severe decrease in SpO2 were also very strong predictors of change in FEV1 in linear regression adjusted for age, gender, and baseline FEV1% predicted.ConclusionIncreased wheezing, as experienced by the patient, and a decreased SpO2 value strongly indicated a drop in lung function during asthma and COPD exacerbations and should probably be taken into account when treatment with oral corticosteroids is considered.

Nocturnal Asthma: A Special Type of Asthma

Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV1) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma. Nocturnal asthma is associated with a circadian pattern in lung function, distal airway inflammation, glucocorticoid receptor affinity, pulmonary capillary blood volume, and beta-2 adrenergic receptor function may also contribute. Knowledge of these characteristics, along with an understanding of the specific therapies directed at the circadian nature of this disease, can result in significant improvements in lung function, sleep quality, and asthma related quality of life.

Do asthma patients with panic disorder really have worse asthma? A comparison of physiological and psychological responses to a methacholine challenge

BackgroundPanic disorder (PD) has been linked to worse asthma outcomes. Some suggest that asthmatics with PD have worse underlying asthma; others argue that worse outcomes are a result of their tendency to over-report symptoms. This study aimed to measure physiological and psychological responses to a simulated asthma attack (methacholine challenge test: MCT) in asthmatics with and without PD. MethodsAsthmatics with (n = 19) and without (n = 20) PD were recruited to undergo a MCT. Patients completed subjective symptom questionnaires (Panic Symptom Scale, Borg Scale) before and after a MCT. Physiological measures including heart rate (HR), and systolic and diastolic blood pressure (SBP/DBP) were also recorded. ResultsAnalyses, adjusting for age and sex, revealed no difference in methacholine concentration required to induce a 20% drop in forced expiratory volume in one second (FEV1: F = 0.21, p = .652). However, PD patients reported worse subjective symptoms, including greater ratings of dyspnea (F = 8.81, p = .006) and anxiety (F = 9.44, p = .004), although they exhibited lower levels of physiological arousal (i.e., HR, SBP/DBP). An interaction effect also indicated that PD, relative to non-PD, patients reported more panic symptoms post-MCT (F = 5.05, p = .031). ConclusionsAsthmatics with PD report higher levels of subjective distress, despite exhibiting lower levels of physiological arousal, with no evidence of greater airway responsiveness. Results suggest that worse outcomes in PD patients may be more likely due to a catastrophization of bodily symptoms, rather than worse underlying asthma. Interventions designed to educate patients on how to distinguish and manage anxiety in the context of asthma are needed.

Effect of prasugrel in patients with asthma: results of PRINA, a randomized, double‐blind, placebo‐controlled, cross‐over study

Although experimental studies have demonstrated that platelets are proinflammatory cells, no randomized studies have tested the anti-inflammatory effect of antiplatelet agents in humans. The platelet P2Y12 receptors mediated bronchial inflammation in a mouse model of asthma, suggesting that P2Y12 represents a pharmacologic target for asthma. In this proof-of concept, placebo-controlled, randomized, cross-over study, we tested the effects of the P2Y12 antagonist prasugrel on bronchial hyperreactivity of asthmatic patients. Twenty-six asthmatic patients were randomly and blindly allocated to prasugrel (10 mg once daily) or placebo for 15 days. After a ≥ 15-day wash-out, patients were crossed over to the alternative treatment. Before and after each treatment, patients underwent a bronchial provocation test with mannitol and measurement of fractional exhaled nitric oxide (FeNO). Inhibition of P2Y12 -dependent platelet reactivity (platelet reactivity index [PRI]) was measured with the vasodilator-stimulated phosphoprotein phosphorylation assay. The provocative dose of mannitol causing a 15% drop in forced expiratory volume in 1 s increased from 142 mg (95% confidence interval [CI] 82-202) to 187 mg (95% CI 113-262) after prasugrel treatment (P = 0.09), and did not change after placebo treatment (136 mg [95% CI 76-196] and 144 mg [95% CI 84-204], P = 0.65). FeNO did not change after either treatment. The PRI decreased from 80% (95% CI 77-83) to 23% (95% CI 7-29) after prasugrel treatment (P < 0.001) and remained unchanged after placebo. Our proof-of-concept, randomized, controlled study is the first one to test in vivo the anti-inflammatory effects of platelet inhibition in human patients. The results suggest that pharmacologic inhibition of P2Y12 receptors may slightly reduce the bronchial inflammatory burden, and lay the groundwork for further studies, with clinical endpoints.

Effectiveness of incentive spirometry in patients following thoracotomy and lung resection including those at high risk for developing pulmonary complications

BackgroundFollowing thoracotomy, patients frequently receive routine respiratory physiotherapy which may include incentive spirometry, a breathing technique characterised by deep breathing performed through a device offering visual feedback. This type of...

Omalizumab Protects against Allergen- Induced Bronchoconstriction in Allergic (Immunoglobulin E-Mediated) Asthma

Background: Omalizumab has been shown to suppress responses to inhaled allergens in allergic asthma patients with pretreatment immunoglobulin E (IgE) ≤700 IU/ml. To extend current dosing tables, we evaluated the potential of high omalizumab doses to block allergen-induced bronchoconstriction in patients with higher IgE levels. Methods: Asthmatic adults (18–65 years; body weight 40–150 kg) were divided into groups according to screening IgE (group 1: 30–300 IU/ml; group 2: 700–2,000 IU/ml) and randomized 2:1 to omalizumab/placebo every 2 or 4 weeks for 12–14 weeks. Allergen bronchoprovocation (ABP) testing was performed before treatment and at weeks 8 and 16. The primary efficacy endpoint, the early-phase allergic response (EAR), was defined as the maximum percentage drop in forced expiratory volume in 1 s during the first 30 min after ABP. Serum free IgE was determined as a pharmacodynamic endpoint, and the exhaled fractional concentration of nitric oxide (FE_NO) was an exploratory endpoint. Results: Fifty patients were included in the study. Omalizumab improved EAR; at week 8, EAR was 23.1% for placebo, 9.3% in group 1 (p = 0.018 versus placebo) and 5.6% in group 2 (p < 0.001). At week 16, EAR was 20%, 11.8% (p = 0.087) and 5.1% (p < 0.001), respectively. Free IgE decreased in groups 1 and 2 and remained <50 ng/ml in all patients during weeks 6–16. Omalizumab completely suppressed FE_NO increases after ABP in both groups. Conclusions: Omalizumab blocked early asthmatic responses over a broad range of IgE/body weight combinations. Extending the dosing tables enables omalizumab to benefit a wider range of patients.

Is a positive nasal lysine‐aspirin challenge test associated with a more severe phenotype of chronic rhinosinusitis and asthma?

Current guidelines recommend a greater use of aspirin challenge testing in the diagnosis of aspirin-intolerant rhinosinusitis and asthma, a disorder with high burden of illness and resistance to treatment. The indications for these tests and their clinical significance remain unclear. This study was designed to characterize the phenotype of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) with or without asthma undergoing a nasal lysine-aspirin (L-ASA) challenge to evaluate which factors strongly predict a positive test. Seventy-five patients with CRSwNP underwent nasal challenge with 16 mg (total) of L-ASA after 30 minutes of acclimatization and diluent challenge. A positive challenge was defined as a 25% drop in total nasal volume measured by acoustic rhinometry. Twenty-three (31%) participants gave a history of aspirin intolerance and 38 (51%) had a positive nasal L-ASA challenge. Upper airway measures (CT scan score, olfaction, polyp grading, peak nasal inspiratory flow, nasal symptoms, etc.) and lower airway measures (methacholine provocative concentration required to produce a 20% drop in forced expiratory volume in 1 second, effective special airway resistance, and spirometry) were not significantly worse in patients with a positive aspirin challenge. Test sensitivity was 48%, specificity was 52%, positive predictive value was 29%, and negative predictive value was 68%. A regression analysis identified forced expiratory flow at 25-75% (FEF(25-75)), history of aspirin intolerance, and duration of rhinosinusitis as significant predictors of a positive aspirin challenge. A positive response to nasal L-ASA challenge is not associated with a more severe phenotype of CRSwNP with or without asthma. A history of aspirin intolerance, duration of rhinosinusitis, and FEF(25-75) predict a greater response to aspirin.

Vocal cord dysfunction in adolescents

Vocal cord dysfunction (VCD) often presents with dramatic and abrupt symptoms. To diagnose VCD, visualization by direct laryngoscopy is required and because patients are usually asymptomatic, a specific method to provoke VCD is needed. Approaches to predict VCD by alterations of the flow-volume loop have been investigated. Adolescents with clinical suspicion of VCD were invited to participate. After an initial pulmonary function test (PFT), direct laryngoscopy was performed. This was followed by a methacholine challenge test (MCT); the methacholine dose causing a 20% drop in forced expiratory volume after 1 sec (FEV(1) ) (PD(20) FEV(1) ) was calculated. Then a second laryngoscopy was conducted. PFT changes before and after MCT were compared with the data of 14 healthy controls (HCs). Thirty-five patients (8-19 years) were investigated. Three showed anatomical alterations. Of the remaining 32 patients, 14 had VCD and 18 had bronchial hyperresponsiveness (non-VCD). In 29 patients with a positive MCT, PD(20) FEV(1) methacholine was significantly lower in VCD compared with non-VCD (VCD 0.24 ± 0.4 mg, non-VCD 0.73 ± 0.73 mg, P = 0.0006). A PD(20) FEV(1) < 0.24 mg methacholine predicted VCD with a sensitivity of 85% and a specificity of 75%. VCD patients showed significantly lower PFT parameters after challenge; FEV(1) : VCD 58.5 ± 20.1%, non-VCD 80.2 ± 18.0%, and HCs 98.7 ± 16.6% (P < 0.0001). The combination of MCT and laryngoscopy may be able to differentiate between VCD and non-VCD. VCD patients showed a positive reaction at lower methacholine doses and displayed greater airway obstruction after MCT. PFTs and MCT do not replace direct laryngoscopy in the diagnosis of VCD in adolescents.

Exercise Challenge Test: Is a 15% Fall in FEV1 Sufficient for Diagnosis?

Introduction. In the exercise challenge test (ECT), a drop in forced expiratory volume in the first second (FEV1) of between 10 and 15% is the determinant variable for a diagnosis of exercise-induced bronchospasm. Hypothesis. The use of FEV1 plus mean forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25–75%) may increase the sensitivity of the ECT in asthmatic children. Specific objective. To compare FEV1 and FEF25–75% changes in a group of asthmatic and healthy children. Methodology. This was a cross-sectional study. Asthmatics were categorized by their severity (GINA) and after 1 month without controller therapy, an ECT was done under standard protocol. As well, a questionnaire about rhinitis and asthma was conducted with the entire population. ROC curves were used for analysis. Results. A total of 147 children (34 healthy and 113 asthmatics, 18 and 58 males, respectively) were evaluated. Divided into healthy children and intermittent, mild and moderate persistent asthmatics, they had similar average ages (9.4, 9.48, 8.97, and 11.2 years, respectively). Using a 15% fall in FEV1, we obtained 29% sensitivity and 100% specificity. However, when we used a 10% fall in FEV1, sensitivity was 47% and specificity was 97%. Adding a 28% fall in FEF25–75%, sensitivity was 52% and specificity was 94%. Conclusion. This study suggests that test sensitivity can increase by using a lower FEV1 cut-off (10%) and adding a 28% fall in FEF25–75%.

Basophil allergen threshold sensitivity, CD-sens, is a measure of allergen sensitivity in asthma

Allergic asthma is IgE-mediated and the IgE-sensitisation is usually demonstrated by skin prick tests (SPT) and IgE antibody determinations in serum. The SPT and IgE-antibody values do not directly predict if the allergy clinically contributes to the asthma. There is therefore a need for new objective tests that may indicate the clinical importance of an IgE-sensitisation. To evaluate basophil allergen threshold sensitivity (CD-sens) as a measure of allergen sensitivity in allergic asthma. Twenty-six subjects with stable, intermittent allergic asthma were tested with SPT and spirometry, and methacholine and allergen inhalation challenges to determine methacholine PD(20) (provocative dose causing a 20% drop in forced expiratory volume in 1 s) and allergen PD(20) . The results were compared with CD-sens and serological parameters, i.e. IgE- and IgG4 antibodies to the relevant allergens. A significant correlation was found between CD-sens and allergen PD(20) (P = 0.01; r = 0.49; n = 26) as well as between CD-sens and the ratio of allergen PD(20) to methacholine PD(20) (P = 0.007; r = 0.52; n = 26). In patients with a moderate to low degree of bronchial hyperresponsiveness there was an excellent correlation (P = 0.0001; r = 0.88, n = 13) between CD-sens and allergen sensitivity. No relation to either allergen PD(20) or the ratio was found for basophil allergen reactivity measured as CD63 up-regulation at high concentrations of the respective allergen. CD-sens was found to be an objective marker of airway allergen sensitivity in stable allergic asthmatics, that may be used to predict airway responsiveness when bronchial challenge tests cannot be performed.

Effect of Oral Magnesium Supplementation on Measures of Airway Resistance and Subjective Assessment of Asthma Control and Quality of Life in Men and Women with Mild to Moderate Asthma: A Randomized Placebo Controlled Trial

Background: Epidemiological data shows low dietary magnesium(Mg) may be related to incidence and progression of asthma. Objective To determine if long term(6.5 month) treatment with oral Mg would improve asthma control and increase serum measures of Mg status in men and women with mild-to-moderate asthma. Subjects: 55 males and females aged 21 to 55 years with mild to moderate asthma according to the 2002 National Heart, Lung, and Blood Institute(NHLBI) and Asthma Education and Prevention Program(NAEPP) guidelines and who used only beta-agonists or inhaled corticosteroids(ICS) as asthma medications were enrolled. Design: Subjects were randomly assigned to consume 340 mg(170 mg twice a day) of Mg or a placebo for 6.5 months. Measurements: Multiple measures of Mg status including serum, erythrocyte, urine, dietary, ionized and IV Mg were measured. Objective: markers of asthma control were: methacholine challenge test(MCCT) and pulmonary function test(PFT) results. Subjective validated questionnaires on asthma quality of life(AQLQ) and control(ACQ) were completed by participants. Markers of inflammation, including c-reactive protein(CRP) and exhaled nitric oxide(eNO) were determined. Results: The concentration of methacholine required to cause a 20% drop in forced expiratory volume in in minute(FEV1) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate(PEFR) showed a 5.8% predicted improvement over time(P = 0.03) in those consuming the Mg. There was significant improvement in AQLQ mean score units(P < 0.01) and in overall ACQ score only in the Mg group(P = 0.05) after 6.5 months of supplementation. Despite these improvements, there were no significant changes in any of the markers of Mg status. Conclusion: Adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.

An Immunoepidemiological Approach to Asthma: Identification of in-Vitro T-Cell Response Patterns Associated With Different Wheezing Phenotypes in Children

Purpose of the Study. To determine if variations in clinical asthma phenotypes are the result of differences in underlying T-cell immune responses to inhalant allergens. Study Population. One hundred forty-seven children (aged 8.6–13.5 years) and 25 of their siblings (aged 7.4–17.4 years) were recruited from 194 members of a birth cohort studied prospectively for asthma development. Methods. Wheeze and asthma were defined by parental questionnaire. Atopy was defined as at least 1 positive skin-prick test for environmental or food allergens. Increased bronchial hyperreactivity (BHR) was defined as a ≥20% drop in forced expiratory volume in 1 second after inhaled histamine up to 7.8 μmol/L. T-cell responses to allergens and mitogens, blood eosinophils, and immunoglobulin E (IgE) were measured and compared with clinical phenotypes. Results. Ninety-five (55.2%) of the children were atopic, sensitized predominantly to house dust mite (42.4%). Asthma was present in 26 (15.1%) children, of whom 22 (85%) were atopic; BHR was present in 62 (35.9%) children, of whom 45 (73%) were atopic. Atopy was associated with T-helper 2 (Th2) cytokine responses (interleukin-4 [IL-4], IL-5, IL-9, IL-13), whereas Th1 responses (IL-10, interferon-γ [IFN-γ], tumor necrosis factor-α [TNF]) occurred in all children. Skin-prick test wheal size was positively associated with house dust mite allergen-induced IL-5 (P &amp;lt; .0001) and IFN-γ (P = .003) and negatively associated with IL-10. Asthma was associated with eosinophilia and elevated house dust mite–specific IL-5, IL-9, IL-13, and IgE. BHR was associated with eosinophilia, elevated allergen-specific IL-5 and IgE, increased total IgE, and a polyclonal cytokine response (IL-5, IL-13, IFN-γ, and TNF-α). In atopics, current asthma or wheeze was associated with house dust mite allergen-specific IL-5 and IL-13; BHR was associated with IL-5 and IgE. In nonatopics, BHR was associated with increased house dust mite allergen-specific and polyclonal IL-10 and polyclonal IFN-γ and TNF-α. Conclusions. In atopic and nonatopic children, distinctive immune-response patterns were identified for asthma and BHR. Immunologic Th1 and Th2 hyperresponsiveness was identified as a hallmark of BHR. Reviewer Comments. Modification of T-cell responses has become an increasingly important focus in the investigation of treatments for atopic disease. Although this study further highlights the prominence of Th2-driven responses in atopic individuals, the results also demonstrate allergen-specific and polyclonal Th1 responses associated with BHR in atopic and nonatopic children. These findings suggest a nonantagonistic interaction between Th1 and Th2 pathways in the production of asthma symptoms. Further understanding of the associations between T-cell response patterns and clinical wheezing phenotypes in children may lead to future asthma therapies in this population.

Avaliação da hiperresponsividade brônquica à solução salina hipertônica em crianças e adolescentes

To assess airway hyperresponsiveness to 4.5% hypertonic saline solution in comparison to that obtained through challenge with other bronchoconstriction agents and in relation to patient allergic sensitization. A cross-sectional, experimental study was conducted, initially involving 85 subjects. After exclusions, the final sample consisted of 62 patients, divided into two groups: a study group of those with asthma (n = 45) and a control group of those with no asthma or allergies (n = 17). Hypertonic saline was nebulized using an ultrasonic nebulizer and administered successively for 0.5, 1, 2, 4 and 8 minutes until a drop in forced expiratory volume in one second of = 15% was achieved in relation to the baseline value. The level of specific immunoglobulin E to Dermatophagoides pteronyssinus level was determined by ImmunoCAP assay and was considered positive when > 0.35 kU/L. In the 36 asthma group subjects presenting a response, the mean drop in forced expiratory volume in one second after hypertonic saline nebulization was 27.4%. None of control group subjects (immunoglobulin E < 0.35 kU/L) presented a positive response to hypertonic saline. The mean forced expiratory volume in one second for control group subjects was 9%. The results of a bronchial provocation test were negative in 9 of the asthma group subjects. The frequency of bronchial provocation test positivity was higher in the subjects presenting elevated levels of specific immunoglobulin E, indicating that there is a relationship between bronchial hyperresponsiveness and the level of specific immunoglobulin E. The sensitivity and specificity of the test were 80% and 92%, respectively. Bronchial provocation with hypertonic saline presents satisfactory sensitivity and specificity. Therefore, in addition to being a low cost procedure that requires very little equipment, it is a useful means of assessing hyperresponsiveness in children and adolescents.

Eficácia do formoterol na reversão imediata do broncoespasmo

To evaluate the effectiveness and onset of action of formoterol delivered by dry-powder inhaler in reversing methacholine-induced bronchoconstriction. Patients presenting a drop in forced expiratory volume in one second > 20% after methacholine inhalation were included. A total of 84 patients were evaluated. All of the participating patients presented respiratory symptoms of unknown origin, which were being investigated. The patients were randomized to receive 200 microg of spray fenoterol (n = 41) or 12 microg of dry-powder inhaler formoterol (n = 43), both administered in order to achieve immediate reversal of methacholine-induced bronchoconstriction. We evaluated the decrease in forced expiratory volume in one second (in relation to the baseline value) after methacholine challenge and the dose of methacholine required to provoke a drop of 20% in forced expiratory volume in one second, as well as the increase in forced expiratory volume in one second (in relation to the baseline value) at five and ten minutes after bronchodilator use. There were no significant differences related to gender, age, weight, height or dose of methacholine required to provoke a drop of 20% in forced expiratory volume in one second. Nor were there any significant differences in terms of baseline or post-methacholine forced expiratory volume in one second. In the fenoterol group, the mean postbronchodilator increase in forced expiratory volume in one second increase was 34% (at five minutes) and 50.1% (at ten minutes), compared with 46.5% (at five minutes) and 53.2% (at ten minutes) in the formoterol group. The bronchodilator effect of formoterol at five and ten minutes after methacholine-induced bronchoconstriction was similar to that of fenoterol. Despite being a long-acting bronchodilator, formoterol also has a rapid onset of action, which suggests that it could be employed as a relief medication in cases of bronchoconstriction occurring during asthma attacks.

Occupational asthma due to manual metal-arc welding of special stainless steels

Occupational asthma (OA) can be induced by fumes of manual metal-arc welding on stainless steel. In recent years, the use of special stainless steels (SSS) with high chromium content has increased. This study presents two cases of OA caused by manual metal-arc welding on SSS. In both cases, the diagnosis of OA was based on respiratory symptoms, occupational exposure and positive findings in the specific challenge tests. In the first case, a 46-yr-old welder had experienced severe dyspnoea while welding SSS (SMO steel), but not in other situations. Challenge tests with both mild steel and stainless steel using a common electrode were negative. Welding SSS with a special electrode caused a delayed 37% drop in forced expiratory volume in one second (FEV1). In the second case, a 34-yr-old male had started to experience dyspnoea during the past few years, while welding especially SSS (Duplex steel). The workplace peak expiratory flow monitoring was suggestive of OA. Challenge tests with both mild steel and stainless steel using a common electrode did not cause bronchial obstruction. Welding SSS with a special electrode caused a delayed 31% drop in FEV1. In conclusion, exposure to manual metal-arc welding fumes of special stainless steel should be considered as a new cause of occupational asthma.