Atmospheric blocking and temperatures in the Antarctic Peninsula.

The Antarctic Peninsula (AP) has displayed a propensity for persistent blocking ridges and anticyclonic conditions, particularly during recent summertime extreme weather events. This study investigates atmospheric blocking patterns over the AP through historical (1981-2010) and future (2071-2100, SSP5-8.5) periods using ERA5 reanalysis and six CMIP6 models, including multi-member realizations from two models totaling ten simulations. We focus particularly on 500 hPa geopotential height (Z500) and near-surface air temperature (T2m) anomalies. The historical analysis highlights significant differences between the CMIP6 models and ERA5 reanalysis, especially in the austral winter, with EC-Earth3 and INM-CM4 models matching closest with the ERA5. Future projections show that while the northern AP and the Drake Passage largely do not exhibit a clear trend towards increased blocking, there are exceptions. The EC-Earth3 model predicts more blocking-like conditions northwest of the AP in summer and a pronounced ridge over the Bellingshausen Sea in winter, indicating a potential increase in blocking events. The INM-CM4 model projects a minor increase in summer Z500 heights off the western and southern AP, without clear blocking patterns over the AP, and negligible winter changes. Localized intensification is noted in the northern parts of the blocking domain and southern AP during extreme blocking conditions. These variations are mirrored in T2m anomalies, suggesting warming in the northern and southern sections of AP but little change elsewhere. The results of this study underscore the need to more accurately capture complex blocking mechanisms and their impacts on regional climate patterns around the AP. We also suggest employing refined blocking definitions and incorporating a broader range of climate models to enhance our understanding of blocking patterns and their impacts in a changing climate.

The effect of spirometry on bronchial and alveolar nitric oxide in subjects with asthma.

OBJECTIVE: The effect of spirometric maneuvers on exhaled nitric oxide (NO) at the constant flow rate of 50 ml/s (FE(NO)) has been studied with equivocal results. Furthermore, the effects of spirometry on bronchial NO flux (J'aw(NO)) and alveolar NO (CA(NO)), two measurements increasingly being used in clinical and research protocols, are unknown. The aim of this study was to evaluate the effect of spirometry on FE(NO), J'aw(NO), and CA(NO) in adults with asthma. METHODS: Forty-four adults with asthma were studied. To assess the impact of exhaled NO measurement itself on exhaled NO values, FE(NO), J'aw(NO), and CA(NO) were obtained twice, at baseline and after a resting period of 10 min. Then spirometry (with or without bronchodilator) was performed followed by exhaled NO measurements at 10 min. RESULTS: In the group with pre-bronchodilator study only (n = 26), mean (95% CI) values before spirometry were 37.3 ppb (22.2-52.4) for FE(NO), 2375 pl/s (1613-3137) for J'aw(NO), and 1.65 ppb (0.95-2.35) for CA(NO), compared with 35.5 ppb (21.1-49.0, p = .10), 2402 pl/s (1663-3141, p = .85), and 1.60 ppb (0.64-2.56, p = .87) after spirometry, respectively. Spirometry-induced changes in exhaled NO values were also not significant in the group with both pre- and post-bronchodilators (n = 18). Furthermore, changes in FE(NO), J'aw(NO), and CA(NO) values were similar in the two groups. CONCLUSIONS: Our findings demonstrate that spirometry (with or without bronchodilator) does not induce significant changes in bronchial NO flux or alveolar NO values. Therefore, exhaled NO values may be obtained after spirometric maneuvers.

Eurytrematosis in cattle in southern Espírito Santo State, Brazil - case report.

This work reports an outbreak of eurytrematosis in cattle in the municipality of Ibitirama, southern Espírito Santo State, Brazil. Six cattle were necropsied from August to December 2019, with finding of Eurytrema coelomaticum in the pancreas. A survey of epidemiological data was carried out on the farms along with coproparasitological examination of cattle from the same herd. Parasites were found in all necropsied animals, with different degrees of parasitism, ranging from mild to massive infection (6 - 2000 specimens). Macroscopic analyses of the pancreas revealed changes in 83.33% (5/6) of the cases, and by microscopy, pancreatic fibrosis ranging from Grade I to Grade III was observed. Inspection of the grazing areas confirmed the presence of two intermediate hosts, a terrestrial snail of the Bradybaena genus, with larval forms of the trematode in histological findings, and a grasshopper of the Conocephalus genus. Although none of the cattle showed clinical signs in the coproparasitological examination, 73.80% (31/42) tested positive for E. coelomaticum eggs. This is the first record of an outbreak of eurytrematosis in cattle in Espírito Santo State, indicating the importance of carrying out diagnosis based on epidemiology and necroscopic and parasitological examinations in animals in the region so that appropriate control measures can be adopted.

Este trabalho objetivou relatar um caso de euritrematose em bovinos no município de Ibitirama, Sul do Estado do Espírito Santo, Brasil. Foram necropsiados seis bovinos de agosto a dezembro de 2019, que apresentaram Eurytrema coelomaticum no pâncreas. Foi realizado levantamento de dados epidemiológicos nas propriedades e exames coproparasitológico em bovinos do mesmo plantel. Em todos os animais necropsiados foram encontrados parasitos, com diferentes graus de parasitismo, variando de infeção branda a maciça (6 - 2000 exemplares). Análises macroscópicas dos pâncreas revelaram alterações em 83,33% (5/6) dos casos e, na microscopia, observou-se fibrose pancreática variando de Grau I a Grau III. A inspeção das áreas de pastejo constatou a presença dos dois hospedeiros intermediários, moluscos terrestres do gênero Bradybaena com formas larvares do trematoda em achados histológicos e gafanhotos do gênero Conocephalus. Nenhum dos bovinos apresentou sinais clínicos, no entanto, no exame coproparasitológico, 73,80% (31/42) testaram positivo para ovos de E. coelomaticum. Este é o primeiro registro de surto de euritrematose em bovinos no estado do Espírito Santo, mostrando a importância da realização do diagnostico a partir da epidemiologia e de exames necroscópicos e parasitológicos em animais da região para que sejam adotadas medidas adequadas de controle.

Home tracheotomy mechanical ventilation in patients with amyotrophic lateral sclerosis: causes, complications and 1-year survival.

BACKGROUND: Home tracheotomy mechanical ventilation (HTMV) can prolong survival in patients with amyotrophic lateral sclerosis (ALS) when non-invasive ventilation (NIV) fails, but knowledge about HTMV is scarce. The aim of this study was to determine the causes of tracheotomy and the main issues of 1-year HTMV in a cohort of patients with ALS. METHODS: A prospective study of all patients needing HTMV was performed in a referral respiratory care unit (RCU) from April 2001 to January 2010. Patients' informed decisions about HTMV were fully respected. Caregivers were trained and could telephone the RCU. Hospital staff made home visits. RESULTS: All patients (n=116) agreed to participate and a tracheotomy was needed for 76, mainly due to bulbar dysfunction. Of the 38 who had a tracheotomy, in 21 it was performed in an acute setting and in 17 as a non-emergency procedure. In 19 patients the tracheotomy was related to the inadequacy of mechanically assisted coughing (MAC) to maintain normal oxygen saturation. During HTMV, 19 patients required hospitalisation, 12 with respiratory problems. The 1-year survival rate was 78.9%, with a mean survival of 10.39 months (95% CI 9.36 to 11.43). Sudden death was the main cause of death (n=9) and only one patient died from respiratory causes. No predictive factors for survival were found. CONCLUSIONS: Besides NIV inadequacy, the ineffectiveness of mechanically assisted coughing appears to be a relevant cause of tracheotomy for patients with ALS with severe bulbar dysfunction. Patients choosing HTMV provided by a referral RCU could have a good 1-year survival rate, respiratory problems being the main cause of hospitalisation but not of death.

The effect of different periods of argon deaeration on exhaled breath condensate pH.

BACKGROUND: Exhaled breath condensate (EBC) pH has been considered as a biomarker of airway inflammation in asthma. However, little information is available on the duration of argon deaeration required to achieve a stable pH in EBC samples. OBJECTIVE: To identify differences in EBC pH after argon deaeration for 2, 4, and 8 min. METHODS: EBC pH was determined in EBC samples from 48 subjects with allergic rhinitis (11 asthmatics) and 14 healthy volunteers without deaeration and after argon deaeration for 2, 4, and 8 min. RESULTS: The mean (95% CI) pH values obtained from samples analyzed after 4 min [7.66 (7.52-7.80)] and 8 min [7.70 (7.55-7.85)] of argon deaeration were significantly less acidic (p < .001) than those identified after 2 min of deaeration [7.53 (7.40-7.66)]; differences between pH values at 4 and 8 min were not significant. Furthermore, changes in EBC pH of nondeaerated samples after 4 and 8 min of deaeration were significantly greater than those after 2 min, the mean difference being 0.11 (95% CI, 0.02-0.20, p < .05) and 0.13 (95% CI, 0.04-0.22, p < .01), respectively; differences between changes at 4 and 8 min were not significant. CONCLUSIONS: Stabilization of EBC pH is achieved after argon deaeration for 4 min. Therefore, this deaeration period may be recommended instead of the 7-8 min used in several studies.

Maximal degree of airway narrowing induced by methacholine and adenosine monophosphate: relationship with the decrease in forced vital capacity.

BACKGROUND: Changes in forced vital capacity (FVC) may represent an indirect method for the detection of plateau in response to inhaled bronchoconstrictor agents. OBJECTIVE: To determine the relationship between the level of plateau obtained with either methacholine or adenosine monophosphate (AMP) and the decrease in FVC induced by each bronchoconstrictor agent. METHODS: Airway responsiveness to high concentrations of methacholine and AMP was determined in patients with intermittent asthma (n = 41) or allergic rhinitis (n = 26). Furthermore, allergen-induced changes in the response to each bronchoconstrictor agent were investigated in 18 pollen-sensitive patients. Concentration-response curves were characterized by the slope of the FVC values recorded at each step of the challenge against the corresponding forced expiratory volume in 1 second (FEV1) values and, if possible, by the level of plateau. RESULTS: The slope FVC vs FEV1 was similar in patients with plateau and in those without plateau. In patients with pollen allergy, the mean (95% confidence interval) for the level of plateau detected with methacholine increased from 16.8% (11.8%-22.0%) before the pollen season to 21.7% (14.8%-28.6%, P = .008) during the pollen season, whereas pollen-induced changes in the slope FVC vs FEV1 were not significant. Similar results were obtained with AMP. CONCLUSIONS: In patients with allergic rhinitis or intermittent asthma, methacholine or AMP-induced changes in FVC are not significantly related to the presence or level of plateau. Furthermore, these 2 constituents of the concentration-response curve can be modified independently by a proinflammatory stimulus. These results suggest that the bronchoconstrictor-induced change in FVC cannot be used as a surrogate estimation of the level of plateau.

Synthesis and evaluation of thermal neutron attenuation properties of lithium orthosilicate for its application as a beam shaping material on BNCT facilities.

Thermal neutron attenuation capacity of Li4SiO4 was evaluated to assess its potential capabilities as a beam shaping material for boron neutron capture therapy (BNCT) facilities. Samples of Li4SiO4 were prepared by two different synthesis methods, using different raw materials and were characterized using x-ray, electron diffraction and transmission electron microscopy. Neutron measurements were performed at the BNCT and the neutron radiography facilities of Centro Atómico Bariloche. Considering its natural isotopic abundance, Li4SiO4 proved to be remarkably effective in comparison with other neutron-absorbing materials. Given the availability of natural Lithium in local salt mines and the scalable feasibility, Li4SiO4 qualifies as a potential material for BNCT beam shaping applications.

A Gadolinium Metal-Organic Framework Film as a Converter Layer for Neutron Detection.

Metal-organic frameworks (MOFs) are known for their versatility in terms of their crystalline structure, porosity, resistance to temperature, radiation damage, and luminescence among others. Gadolinium (Gd) is one of the elements with the highest reported cross-section for low energy neutron capture, producing internal conversion electrons and γ rays as a result of the neutron absorption. The development of Gd-BTC films (BTC=1,3,5-benzenetricarboxylate) is shown that were deposited on Si and Al substrates by airbrushing, and characterized by profilometry, Raman, EDX and X-ray diffraction. Radiation damage, thermal decomposition and neutron absorption of these films were studied as well. Gd-BTC films were attached to CMOS devices (Complementary Metal-Oxide-Semiconductor), which are sensible to the internal conversion electrons, in order to build a neutron detector. The devices Gd-BTC/CMOS could selectively detect neutrons in the presence of γ rays with a thermal neutron detection efficiency of 3.3±0.1 %, a signal to noise ratio of 6 : 1, and were suitable to obtain images.

Importance of noninvasively measured respiratory muscle overload among the causes of hospital readmission of COPD patients.

AIM: To evaluate the influence of respiratory muscle overload and right cardiac overload among the possible risk factors of hospital readmission in a 1-year follow-up of a cohort of patients with moderate-to-severe COPD. METHODS: A total of 112 COPD patients who were admitted consecutively to the hospital for acute exacerbation. At hospital discharge, we evaluated the conventional clinical and functional determinations in addition to the pressure-time index (PTI), which is obtained using the equation PTI = (Pawo/Pimax) x (Ti/Ttot) x 100, where Pawo represents the mean airway pressure measured at the mouth during spontaneous breathing, Pimax is the maximal inspiratory pressure, Ti is the inspiratory time, and Ttot is the total breathing cycle time. A cardiac echo-Doppler examination was carried out when patients were in stable condition and presented clinical signs of right cardiac overload prior to inclusion in the study. RESULTS: Multivariate analysis showed that the use of long-term oxygen therapy (LTOT) and high PTI (> 0.25) were independently related to the risk of hospital readmission. Patients receiving LTOT had higher Paco(2) (p < 0.05), FEV(1) percent predicted (p < 0.05), FVC percent predicted (p < 0.05), and Pao(2) (p < 0.05), and had higher Paco(2) (p < 0.05). An elevated systolic pulmonary arterial pressure (> 40 mm Hg) was also independently related, but only 28 patients had echo-Doppler data that could be used. CONCLUSIONS: At hospital discharge, noninvasively measured respiratory muscle overload as well as the use of LTOT were associated with an increased risk of hospital readmission for exacerbation in patients with moderate-to-severe COPD.

Differences in the response to methacholine between the tidal breathing and dosimeter methods: influence of the dose of bronchoconstrictor agent delivered to the mouth.

BACKGROUND: It has been postulated that differences in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) values between the dosimeter method and tidal breathing method might be due to differences in the dose of agonist delivered to the mouth. The aim of the present study was to determine the influence of the dose of aerosol delivered to the mouth on differences in the response obtained with each challenge method. METHODS: This study measured airway responsiveness to methacholine by dosimeter method and tidal breathing method in 27 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method. Concentration-response curves were characterized by the PC20. RESULTS: The dosimeter method PC20 was significantly higher than the tidal breathing method PC20, with geometric mean values of 4.03 (95% confidence interval [CI], 1.86 to 8.78 mg/mL) and 2.19 (95% CI, 1.32 to 3.64 mg/mL; p = 0.04), respectively. The mean difference in the PC20 value detected with each method was similar in subjects with tidal breathing method PC20 values > or = 2 mg/mL (0.77 doubling concentrations) and in those with PC20 values < 2 mg/mL (0.96 doubling concentrations; p = 0.83). CONCLUSIONS: The tidal breathing method produces PC20 values significantly lower than a modified dosimeter method, which delivers the same volume of aerosol. These results suggest that the discordant PC20 values obtained with the two methods are not due to differences in the dose of agonist delivered to the mouth.

Effectiveness of assisted and unassisted cough capacity in amyotrophic lateral sclerosis patients.

Decreased cough capacity during a respiratory infection is one of the main causes of acute respiratory failure and hospitalisation in amyotrophic lateral sclerosis (ALS). OBJECTIVE: To determine whether a respiratory measurement could identify the effectiveness of cough capacity in ALS during a respiratory infection. METHODS: This was a prospective study of all ALS patients who were treated at a respiratory care unit due to a respiratory infection from 2012 to 2016. The effectiveness of unassisted and assisted coughing was evaluated and respiratory function tests were performed during the acute episode. RESULTS: Forty-eight ALS patients were enrolled, with only four having an effective unassisted cough. The variable which predicted unassisted cough effectiveness was peak cough flow (PCF) (OR 4499.27; 95%CI 3.60-3219086.19; p = 0.022) with a cut-off point of 2.77 L/s (166 L/min). For manually assisted coughing, the predictor of cough effectiveness was manually assisted PCF (cut-off point of 2.82-169 L/min) (OR 2198.602; 95% CI 3.750-1351691.42; p = 0.019). Mechanically assisted PCF (cut-off point of 2.95-177 L/min) was found to be the predictor of mechanically assisted coughing effectiveness (OR 23.40; 95% CI 2.11-258.96; p = 0.010). CONCLUSIONS: During a respiratory infection in ALS patients, the effectiveness of assisted and unassisted cough capacity depends on the PCF generated.

Bulbar impairment score predicts noninvasive volume-cycled ventilation failure during an acute lower respiratory tract infection in ALS.

UNLABELLED: Amyotrophic lateral sclerosis (ALS) patients can suffer episodes of lower respiratory tract infections (LRTI) leading to an acute respiratory failure (ARF) requiring noninvasive ventilation (NIV). AIM: To determine whether clinical or functional parameters can predict noninvasive management failure during LRTI causing ARF in ALS. MATERIAL AND METHOD: A prospective study involving all ALS patients with ARF requiring NIV in a Respiratory Care Unit. NIV was provided with volume-cycled ventilators. RESULTS: 63 ALS patients were included (APACHE II: 14.93±3.56, Norris bulbar subscore (NBS): 18.78±9.68, ALSFRS-R: 19.90±6.98, %FVC: 40.01±18.07%, MIC: 1.62±0.74L, PCF 2.51±1.15L/s, PImax -34.90±19.44cmH2O, PEmax 51.20±28.84cmH2O). In 73.0% of patients NIV was successful in averting death or endotracheal intubation. Differences were found between the success and failure in the NBS (22.08±6.15 vs 8.66±3.39, p<0.001), ALSFRS (22.08±6.11 vs 12.71±4.39, p<0.001), PCFMI-E (3.85±0.77 vs 2.81±0.91L/s, p=0.007) and ALS onset (spinal/bulbar 33/13 vs 7/10, p=0.03). The predictor of NIV failure was the NBS (OR 0.53, 95% CI 0.31-0.92, p 0.002) with a cut-off point of 12 (S 0.93; E 0.97; PPV 0.76; NPV 0.97). CONCLUSIONS: NBS can predict noninvasive management failure during LRTI in ALS.

Tolerance of Volume Control Noninvasive Ventilation in Subjects With Amyotrophic Lateral Sclerosis.

BACKGROUND: Noninvasive ventilation (NIV) tolerance has been identified as an independent predictor of survival in amyotrophic lateral sclerosis (ALS). Volume control continuous mandatory ventilation (VC-CMV) NIV has been associated with poor tolerance. The aim of this study was to determine the tolerance of subjects with ALS to VC-CMV NIV. METHODS: This was a prospective study involving subjects with ALS who were treated with VC-CMV NIV. Respiratory and functional parameters were recorded when the subjects began ventilatory support. NIV tolerance was evaluated after 3 months. RESULTS: Eighty-seven subjects with ALS were included. After 3 months, 80 subjects (92%) remained tolerant of NIV. Tolerant subjects presented greater survival (median 22.0 months, 95% CI 14.78-29.21) than intolerant subjects (median 6.0 months, 95% CI 0.86-11.13) (P = .03). The variables that best predicted NIV tolerance were mechanically assisted cough peak flow (P = .01) and percentage of time spent with SpO2 < 90% at night while on NIV (P = .03) CONCLUSIONS: VC-CMV NIV provides high rates of NIV tolerance in subjects with ALS. Mechanically assisted cough peak flow and percentage of time spent with SpO2 < 90% at night while using NIV are the 2 factors associated with tolerance of VC-CMV NIV in subjects with ALS.

Predictors of need for noninvasive ventilation during respiratory tract infections in medically stable, non-ventilated subjects with amyotrophic lateral sclerosis.

BACKGROUND: Acute lower respiratory infections can impair muscle strength in patients with amyotrophic lateral sclerosis (ALS). When associated with an increase in load on the respiratory system, this situation may precipitate hypercapnic respiratory failure in non-ventilated patients with ALS. The aim of this study was to determine whether a clinical or functional parameter can predict the need for noninvasive ventilation (NIV) during an acute respiratory infection for medically stable, non-ventilated patients with ALS. METHODS: This was a prospective study involving all non-ventilated subjects with ALS admitted due to an acute respiratory infection to a respiratory care unit from a tertiary hospital. RESULTS: Thirty-two non-ventilated subjects with ALS were admitted to our respiratory care unit due to an acute respiratory infection: 60.72 ± 10.54 y, 13 males, 23 with spinal onset, FVC of 1.58 ± 0.83 L, FVC of 56.21 ± 23.15% of predicted, peak cough flow of 3.41 ± 1.77 L/s, maximum insufflation capacity of 1.87 ± 0.94 L, revised Amyotrophic Lateral Sclerosis Functional Rating Scale score of 22.80 ± 8.83, and Norris bulbar score of 23.48 ± 12.14. Fifteen subjects required NIV during the episode. Logistic regression analysis showed that the only predictors of need for NIV were percent-of-predicted FVC (odds ratio of 1.06, 95% CI 1.01-1.11, P = .02) and peak cough flow (odds ratio of 2.57, 95% CI 1.18-5.59, P = .02). CONCLUSIONS: In medically stable, non-ventilated patients with ALS, measurement of percent-of-predicted FVC and peak cough flow can predict the need for NIV during an acute lower respiratory tract infection.

Efficacy of mechanical insufflation-exsufflation in medically stable patients with amyotrophic lateral sclerosis.

OBJECTIVE: To determine under what circumstances the use of mechanical insufflation-exsufflation (MI-E) can generate clinically effective expiratory flows for airway clearance (> 2.7 L/s) for clinically stable patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHOD: Twenty-six consecutive patients with ALS were studied, 15 with severe bulbar dysfunction. Using a pneumotachograph and with the aid of an oronasal mask, we measured FVC, FEV(1), peak cough flow (PCF), maximum insufflation capacity (MIC), PCF generated from a maximum insufflation MIC (PCFMIC), and PCF generated by MI-E (PCFMI-E). MI-E was delivered at +/- 40 cm H(2)O. Maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) at the mouth were also measured. RESULTS: Although both groups had a similar time from ALS symptom onset to diagnosis, statistical differences (p < 0.05) were found between nonbulbar and bulbar patients in lung function and cough capacity parameters: FVC, 2.58 +/- 1.24 L vs 1.62 +/- 0.74 L; FEV(1), 2.26 +/- 1.18 L vs 1.54 +/- 0.69 L; PImax, - 93.45 +/- 47.47 cm H(2)O vs - 3.64 +/- 25.07 cm H(2)O; PEmax, 140.45 +/- 75.98 cm H(2)O vs 69.93 +/- 32.14 cm H(2)O; MIC, 3.02 +/- 1.22 L vs 1.97 +/- 0.75 L; PCF, 5.91 +/- 2.55 L/s vs 3.42 +/- 1.44 L/s; PCFMIC, 6.68 +/- 2.71 L/s vs 4.00 +/- 1.48 L/s; and PCFMI-E, 4.34 +/- 0.82 L/s vs 3.35 +/- 0.77 L/s. Four patients with bulbar dysfunction and MIC > 1 L had PCFMI-E < 2.7 L/s. The receiver operating characteristic (ROC) curve analysis showed PCFMIC of 4 L/s predicting those patients with PCFMIC greater than PCFMI-E. CONCLUSION: MI-E is able to generate clinically effective PCFMI-E (> 2.7 L/s) for stable patients with ALS, except for those with bulbar dysfunction who also have a MIC > 1 L and PCFMIC <2.7 L/s who probably have severe dynamic collapse of the upper airways during the exsufflation cycle. Clinically stable patients with mild respiratory dysfunction and PCFMIC > 4 L/s might not benefit from MI-E except during an acute respiratory illness.

Effect of salmeterol on seasonal changes in airway responsiveness and exhaled nitric oxide in pollen-sensitive asthmatic subjects.

OBJECTIVE: Using a model of natural allergen exposure, we examined the effect of regular treatment with salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO). DESIGN: Double-blind, randomized, parallel-group study. SETTING: Specialist allergy unit in a university hospital. PATIENTS: Asthmatic patients sensitized to pollen allergens were randomly allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13). INTERVENTIONS: Salmeterol, 25 micro g, and placebo inhalers, two puffs bid, for 6 weeks. MEASUREMENTS: Spirometry, the level of a provocative concentration of a substance (methacholine) causing a 20% fall in FEV(1) (PC(20)), the PC(20) level for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen season and were repeated at the height of the pollen season after 6 weeks of treatment with salmeterol or placebo. RESULTS: The decrease in FEV(1) during the pollen season was significantly larger in the placebo group than in the salmeterol group, the mean difference in the change between the groups being 0.20 L (95% confidence interval, 0.03 to 0.35; p = 0.047). Changes in PC(20) for methacholine, PC(20) for AMP, and ENO levels were not significantly different between treatment groups. However, a mean (+/- SEM) decrease in the PC(20) for methacholine of -1.0 +/- 0.4 doubling concentrations was observed within the placebo group (p = 0.03), whereas no significant changes were observed within the salmeterol group. A significant decrease in PC(20) for AMP (doubling concentrations) was observed within the placebo group (-2.1 +/- 0.6; p = 0.003) and the salmeterol group (-1.5 +/- 0.4; p = 0.003). ENO concentrations increased significantly among the placebo and the salmeterol groups during natural pollen exposure. CONCLUSION: These observations indicate that natural allergen exposure and the regular use of salmeterol are not associated with a greater increase in ENO and airway responsiveness than allergen exposure alone.

Kyphoscoliotic ventilatory insufficiency: effects of long-term intermittent positive-pressure ventilation.

OBJECTIVES: To determine the effects of long-term nocturnal intermittent positive-pressure ventilation (NIPPV) on symptoms, pulmonary function test results, sleep, and respiratory muscle performance in patients with ventilatory insufficiency due to severe kyphoscoliosis. DESIGN: A prospective study in which 16 severe kyphoscoliotic patients were treated with NIPPV delivered by volume-cycled and pressure-cycled ventilators, over a period of 36 months. INTERVENTIONS AND MEASUREMENTS: At baseline, pulmonary function tests, blood gas measurements, polysomnography, and respiratory muscle strength (measured by noninvasive indexes) were obtained. Symptoms and the number of hospitalizations in the previous 6 months also were recorded. Patients then began using a ventilator for > 1 to 2 days, in order to select the type of ventilator and the appropriate interface. Patients returned for evaluation (in outpatient setting) every 6 months for a follow-up period of 3 years. At 6 months, polysomnography was repeated, and by the third year clinical and functional parameters had been reassessed. RESULTS: All symptoms improved significantly with NIPPV therapy, when compared with the baseline values. The mean (+/- SD) PaO(2) and FVC values increased at 36 months compared with baseline values (62.6 +/- 7.1 vs 67.8 +/- 8.8 mm Hg, respectively; and 37.9 +/- 7.2% vs 47.5 +/- 11.9%, respectively; p < 0.05 for both). There were significant improvements in mean maximal inspiratory pressure (55.8 +/- 17.4 to 78.5 +/- 17.5 cm H(2)O), maximal expiratory pressure (53.8 +/- 17.7 to 72.3 +/- 11.0 cm H(2)O), mouth pressure (0.28 +/- 0.08 to 0.22 +/- 0.02 cmH(2)O), and pressure-time index (0.18 +/- 0.05 to 0.11 +/- 0.02; p < 0.05 for all comparisons). There were no significant differences in breathing pattern and ventilatory drive. After 6 months, nocturnal oxyhemoglobin saturation improved, however, there was no significant change in sleep architecture. All patients subjectively perceived a better quality of life after beginning ventilation, which persisted over the course of the study. CONCLUSIONS: Long-term NIPPV therapy improves daytime blood gas levels, respiratory muscle performance, and hypoventilation-based symptoms in patients with severe kyphoscoliosis.

The effect of challenge method on methacholine-induced changes in sensitivity and air trapping.

BACKGROUND: The methacholine challenge test performed with the tidal breathing method induces a greater fall in FEV(1) than the dosimeter method; however, the effect of the challenge method on methacholine-induced fall in FVC has not been investigated. OBJECTIVE: To determine the influence of the challenge method on methacholine-induced changes in FEV(1) and FVC. METHODS: Airway responsiveness to methacholine was determined by dosimeter method and tidal breathing method in 37 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method and the same nebulizer model was used for the two challenges. The response was expressed by the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) and by the percent fall in FVC at the PC(20) value relative to FVC after saline inhalation. RESULTS: The PC(20) values obtained with the tidal breathing method and the dosimeter method were similar, with geometric mean values of 3.15 (95%CI, 1.85-5.34 mg/mL) and 2.51 (1.37-4.61 mg/mL, P = 0.092), respectively. The percent fall in FVC at the PC(20) value obtained with the dosimeter was significantly greater than that obtained with the tidal breathing method, with mean values of 11.8 (95%CI, 10.0-13.5%) and 9.4 (95%CI, 8.1-10.8, P = 0.002), respectively. CONCLUSIONS: Differences in methacholine PC(20) values obtained with the two challenge methods recommended in guidelines may be overcome by introducing some technical modifications in the dosimeter method. However, the technical factors that affect methacholine sensitivity and air trapping are at least partially different.

Effects of allergen exposure on methacholine and AMP-induced air trapping in pollen-sensitive subjects.

BACKGROUND: The effect of pro-inflammatory stimuli on bronchoconstrictor-induced air trapping has not been studied. OBJECTIVE: To determine the effect of natural allergen exposure, a pro-inflammatory stimulus, on methacholine- and adenosine 5'-monophospate (AMP)-induced air trapping. METHODS: Airway responsiveness to methacholine and AMP before and during the pollen season was obtained in 25 subjects with pollen allergy and in 10 healthy controls. The response was expressed by the sensitivity (PC20 value) and by the slope and intercept of the FVC values recorded at each step of the challenge against the corresponding FEV1 values. RESULTS: The slope and intercept FVC versus FEV1 values for both methacholine and AMP were significantly higher in subjects with pollen allergy than in healthy controls. In the group with pollen allergy, both methacholine and AMP PC20 values decreased significantly during the pollen season. However, the mean (95% CI) slope FVC versus FEV1 values for methacholine were 1.00 (0.84-1.16) before the pollen season and 0.99 (0.86-1.12, P = 0.90) during the pollen season. Similar results were obtained with AMP. CONCLUSIONS: Although the air trapping induced by both methacholine and AMP is significantly greater in subjects with pollen allergy than in healthy controls, natural allergen exposure is associated with a selective increase in airway sensitivity without concomitant changes in bronchoconstrictor-induced air trapping. These findings suggest that the information provided by the bronchoconstrictor-induced change in FEV1 and FVC is not equivalent and may be complementary.