The impact of diabetes and age on pulmonary function: Data from the National Health and Nutrition Examination Survey

Using data from NHANES III, we evaluated the effect of diabetes on the age-related decline in lung function. The Diabetes group (n = 471) had significantly lower mean FEV₁ and FVC values than the No Diabetes group (n = 4317), but pulmonary function declined with increasing age at a similar rate for both groups.     

Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: The PLATINO study

BackgroundAcute bronchodilator responsiveness is an area of discussion in COPD. No information exists regarding this aspect of the disease from an unselected COPD population. We assessed acute bronchodilator responsiveness and factors influencing it in subjects with and without airway obstruction in an epidemiologic sample.MethodsCOPD was defined by GOLD criteria (post-bronchodilator FEV₁/FVC < 0.70). In this analysis, subjects with pre-bronchodilator FEV₁/FVC <0.70 but ≥0.70 post-bronchodilator were considered to have reversible obstruction. Bronchodilator responsiveness after albuterol 200 μg was assessed using three definitions: a) FVC and/or FEV₁ increment ≥12% plus ≥200 mL over baseline; b) FEV₁ ≥ 15% increase over baseline; and c) FEV₁ increase ≥10% of predicted value.ResultsThere were 756 healthy respiratory subjects, 481 subjects with reversible obstruction and 759 COPD subjects. Depending on the criterion used the proportion of person with acute bronchodilator responsiveness ranged between 15.0–28.2% in COPD, 11.4–21.6% in reversible obstructed and 2.7–7.2% in respiratory healthy. FEV₁ changes were lower (110.6 ± 7.40 vs. 164.7 ± 11.8 mL) and FVC higher (146.5 ± 14.2 mL vs. ?131.0 ± 19.6 mL) in COPD subjects compared with reversible obstructed. Substantial overlap in FEV₁ and FVC changes was observed among the groups. Acute bronchodilator responsiveness in COPD persons was associated with less obstruction and never smoking.ConclusionsOver two-thirds of persons with COPD did not demonstrate acute bronchodilator responsiveness. The overall response was small and less than that considered as significant by ATS criteria. The overlap in FEV₁ and FVC changes after bronchodilator among the groups makes it difficult to determine a threshold for separating them.     

Association between low pulmonary function and metabolic risk factors in Korean adults: the Korean National Health and Nutrition Survey

Impaired lung function is a risk factor for cardiovascular events and mortality. In addition, lung function impairment is also associated with insulin resistance and type 2 diabetes mellitus. It is well known that a common mechanism, such as insulin resistance and obesity, underlies metabolic syndrome. Our aim was to evaluate the association between impaired lung function and metabolic risk factors using data from a nationwide survey of chronic obstructive pulmonary disease prevalence in Korea and the Korean National Health and Nutrition Survey in 2001. The study population included 4001 subjects (aged ≥18 years) who underwent spirometry at least twice. We analyzed the association of low pulmonary function with metabolic syndrome components using multiple linear regression and also analyzed the association of metabolic syndrome with restrictive lung disease and obstructive lung disease using multiple logistic regression adjusted for waist to height ratio, sex, age, smoking, and the other covariates. Waist girth, systolic blood pressure, and triglyceride were associated with forced vital capacity (FVC); and only triglyceride was so with forced expiratory volume in 1 second (FEV₁), but not with FEV₁/FVC ratio. The odds ratio of metabolic syndrome for restrictive lung disease (FVC <80%, FEV₁/FVC >0.7) was 1.40 (95% confidence interval, 1.01-1.98), and that for obstructive lung disease (FEV₁/FVC <0.7) was 0.93 (95% confidence interval, 0.67-1.28) after adjustment for covariates. These results indicate that low pulmonary function in the general population is associated with clustering of metabolic syndrome risk factors and, furthermore, that restrictive lung disease is also related to metabolic syndrome.     

Trends of COPD in Spain: Changes Between Cross Sectional Surveys 1997, 2007 and 2017

IntroductionWe aim to describe the changes in prevalence and risk factors associated to chronic obstructive pulmonary disease (COPD) in Spain, comparing three population-based studies conducted in three timepoints.MethodsWe compared participants from IBERPOC conducted in 1997, EPISCAN conducted in 2007 and EPISCAN II in 2017. COPD was defined as a postbronchodilator FEV₁/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV₁/FVC below the lower limit of normal (LLN).ResultsCOPD prevalence in the population between 40 and 69 years decreased from 21.6% (95% CI 20.7%–23.2%) in 1997 to 8.8% (95% CI 8.2%–9.5%) in 2017, a 59.2% decline (p < 0.001).In 2007, the prevalence was 7.7% (95% CI 6.8%–8.7%) with an upward trend of 1.1 percentage points in 2017 (p = 0.073). Overall COPD prevalence decreased in men and women, although a significant increase was observed in the last decade in females (p < 0.05). Current smokers significantly increased in the last decades (25.4% in 1997, 29.1% in 2007 and 23.4% in 2017; p < 0.001). Regrettably, COPD underdiagnosis was constantly high, 77.6% in 1997, 78.4% in 2007, and to 78.2% in 2017 (p = 0.95), higher in younger ages (40–49 yrs and 50–59 yrs) and also higher in women than in men in all three studies (p < 0.05).ConclusionsWe report a significant reduction of 59.2% in the prevalence of COPD in Spain from 1997 to 2017 in subjects aged 40–69 years. Our study highlights the significant underdiagnosis of COPD, particularly sustained in women and younger populations.     

Resultados funcionales del trasplante pulmonar en la enfermedad pulmonar obstructiva crónica

IntroductionLung transplantation (LT) is a therapeutic option with controversial results in chronic obstructive pulmonary disease (COPD). We aimed to analyze the outcomes of transplantation in terms of lung function and to identify prognostic factors.MethodA retrospective analysis of 107 patients with COPD receiving lung transplants in the La Fe Hospital between 1991 and 2008 was performed. Preoperative variables, pulmonary function tests before and after LT, surgical procedure variables and long-term monitoring, expressed as mean or percentage, as applicable, were analyzed. Spirometric results before and after LT were analyzed. Linear or logistic regression were used for multivariate analysis depending on the variable.ResultsNinety-four men (87.9%) and 13 women (12.1%) were transplanted, with a mean age ± standard deviation of 52.58 ± 8.05 years; 71% of LTs were double-lung transplantations. Spirometric values improved after LT: FVC: +1.22 L (+34.9%), FEV₁: +1.66 L (+56.7%) and FEF_25-75: +1.85 L (+50.8%); P = .001. This functional improvement was maintained after 5 years only in the group with BODE score > 7 (P = .001). Recipient height, type of LT, use of extracorporeal circulation during the surgical procedure, presence of bronchiolitis obliterans syndrome and the age and cause of death of the donor significantly influenced lung function over time.ConclusionsLT improves lung function in COPD patients. This improvement was maintained at 5 years only in patients with BODE > 7. Double lung transplantation provides better functional results than single-lung transplantation.     

Faster onset of action of formoterol versus salmeterol in patients with chronic obstructive pulmonary disease: A multicenter,randomized study

BackgroundChronic obstructive pulmonary disease (COPD) is a growing public health problem that has increased in recent years. It similarly affects men and women, especially those who smoke. The goals of COPD pharmacotherapy are to improve lung function, reduce symptoms, prevent exacerbations, and improve patients' health status. Bronchodilators are the foundation of treatment for COPD, and the long-acting β₂-agonists formoterol and salmeterol are both indicated for regular use by patients with stable COPD.ObjectiveA clinical study was conducted to compare the onset of bronchodilator effects following treatment with formoterol 12 μg administered twice-daily (BID) or salmeterol 50 μg BID. The trial also assessed whether the bronchodilator effects of treatment resulted in significant differences in clinical response.MethodsThis was a randomized, multicenter, open-label, parallel-group study of formoterol 12 μg BID versus salmeterol 50 μg BID, both administered for 28 days. Patients were current or previous smokers aged ≥40 years, with a diagnosis of stable COPD. The primary efficacy variable was change from baseline in forced expiratory volume in 1 s (FEV₁) 5 min after drug administration on day 28. Secondary efficacy variables included changes from baseline in the 6-min walk test (6MWT) and rescue medication use. The primary variable was assessed by analysis of covariance, with baseline FEV₁ as the covariate.ResultsA total of 270 patients were randomized to formoterol 12 μg BID (n = 137) or salmeterol 50 μg BID (n = 133). In the intent-to-treat population the least square (LS) mean change from baseline in FEV₁ at 5 min postdose on day 28 was 0.13 L in the formoterol group compared with 0.07 L in the salmeterol group (P = 0.022). At 30 min postdose on day 28, the LS mean change from baseline in FEV₁ was 0.17 L in the formoterol group compared with 0.07 L in the salmeterol group (P < 0.001). Similar changes were reported at 60 min postdose (0.19 L for the formoterol group versus 0.13 L for the salmeterol group, P = 0.069). Patients in the formoterol group walked longer distances in the 6MWT and used less rescue medication compared with patients in the salmeterol group, although the differences were not statistically significant.ConclusionsSignificantly greater improvements from baseline in FEV₁ were observed at 5 and 30 min postdose with formoterol 12 μg compared with salmeterol 50 μg after 28 days of treatment. Numeric improvements in the 6MWT and rescue medication use were also observed with formoterol.     

Lung Functions of Japanese Patients with Chronic Rhinosinusitis Who Underwent Endoscopic Sinus Surgery

Background:Chronic rhinosinusitis (CRS), which is clinically classified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), shows considerable geographic differences and heterogeneity. Eosinophilic (E) CRS with nasal polyps (ECRSwNP) has a higher degree of disease severity and higher frequency of comorbid asthma. Epidemiologic studies in different ethnic populations have improved understanding of the pathophysiology of the disease. Here we report the clinical characteristics of Japanese patients with medically refractory CRS undergoing endoscopic sinus surgery (ESS).Methods:We recruited a total of 210 CRS patients and assessed them by nasal endoscopy, the Lund-Mackay score using computed tomography (CT), peripheral eosinophilia and smoking status. We also examined the comorbidity of asthma, effects of age and lung functions in the patients.Results:In this study, 13% of CRSwNP patients and 20% of CRSwNP patients with peripheral blood eosinophilia exhibited obstructive lung dysfunction (FEV₁/FVC < 70%) despite the absence of an asthma diagnosis. Among elderly nonsmoker patients (≥ 60 years) who had never been diagnosed with asthma, 50% of CRSwNP patients with peripheral blood eosinophilia showed decreased FEV₁/FVC < 70%.Conclusions:Our findings suggest that asthma is under-diagnosed in CRS patients who undergo ESS, especially the elderly. Although the association between CRS and asthma has been recognized, increased attention to the comorbidity of obstructive airway diseases such as asthma is still needed for management of medically refractory CRS.     

Resting Lung Function in the Assessment of the Exercise Capacity in Patients With Chronic Heart Failure

BackgroundDespite the lung involvement in patients with chronic heart failure (CHF), the significance of lung function abnormalities to functional status in these patients is still controversial. We postulated that in patients with CHF, resting lung function assessment may provide information of clinical relevance on exercise capacity, expressed as peak oxygen uptake (VO₂) and ventilatory response to CO₂ production (VE/VCO₂) during a maximal exercise.MethodsWe studied 49 clinically stable patients with CHF (38 men, age range: 25–178 years) (New York Heart Association class range: I-IV) with left ventricular ejection fraction < 40%. Patients with chronic obstructive pulmonary disease were excluded. Patients performed pulmonary function tests and maximal incremental exercise test.ResultsResting spirometry was related to the exercise capacity (P < 0.05), expressed as peak VO₂. By means of receiver operating characteristic curve analysis, the forced expiratory volume at first second (FEV₁) cutoff point, which better identified patients with a peak VO₂ ≤ 14 mL/kg/min, was < 79% of predicted value (0.79 sensitivity and 0.73 specificity). Resting lung diffusion capacity for carbon monoxide and end-tidal pressure of CO₂ (PETCO₂) were inversely correlated to VE/VCO₂ (P < 0.01). The lung diffusion capacity for carbon monoxide and PETCO₂ cutoff points, which better identified patients with VE/VCO₂ value > 34, were < 58% of predicted (0.92 sensitivity and 0.42 specificity) and < 33 mm Hg (0.67 sensitivity and 0.92 specificity), respectively.ConclusionsIn patients with CHF, resting lung function, including spirometry, lung diffusion capacity, and PETCO₂, can provide clinically useful information on exercise capacity, by predicting peak VO₂ and VE/VCO₂ slope. The results of this study highlight the role of resting lung function in the assessment of the functional status of cardiac patients.     

Development of Lung Function in Preterm Infants During the First Two Years of Life

IntroductionIt remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size.AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period.MethodsThis observational longitudinal study assessed lung function in 74 preterm (30 + 0 to 35 + 6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF_25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age.ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV_0.5 and forced expiratory flows was seen in preterm infants.ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.     

Utility of bronchodilator response for asthma diagnosis in Latino preschoolers

BackgroundAsthma diagnosis in preschoolers is mostly based on clinical evidence, but a bronchodilator response could be used to help confirm the diagnosis. The objective of this study is to evaluate the utility of bronchodilator response for asthma diagnosis in preschoolers by using spirometry standardised for this specific age group.MethodsA standardised spirometry was performed before and after 200 mcg of salbutamol in 64 asthmatics and 32 healthy control preschoolers in a case-control design study.ResultsThe mean age of the population was 4.1 years (3–5.9 years) and 60% were females. Almost 95% of asthmatics and controls could perform an acceptable spirometry, but more asthmatics than controls reached forced expiratory volume in one second (FEV₁) (57% vs. 23%, p = 0.033), independent of age. Basal flows and FEV₁ were significantly lower in asthmatics than in controls, but no difference was found between groups in forced vital capacity (FVC) and FEV in 0.5 s (FEV_0.5). Using receiver operating characteristic (ROC) curves, the variable with higher power to discriminate asthmatics from healthy controls was a bronchodilator response (% of change from basal above the coefficient of repeatability) of 25% in forced expiratory flow between 25% and 75% (FEF_25–75) with 41% sensitivity, 80% specificity. The higher positive likelihood ratio for asthma equalled three for a bronchodilator response of 11% in FEV_0.5 (sensitivity 30%, specificity 90%).ConclusionsIn this sample of Chilean preschoolers, spirometry had a very high performance and bronchodilator response was very specific but had low sensitivity to confirm asthma diagnosis.     

Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study

IntroductionThe role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response.MethodsObservational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests.ResultsThe study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p < 0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV₁, FEV₁/FVC and FENO, whereas they were FEV₁/FVC and FENO for mannitol. A FENO value > 26 ppb, FEV1 ≤ 103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value > 26 ppb was enough to correctly classify 81.5% of mannitol responders.ConclusionsOur study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values.     

Tiotropium induced bronchodilation and protection from dynamic hyperinflation is independent of extent of emphysema in COPD

BackgroundThe magnitude of tiotropium (1) induced bronchodilation and (2) protection against dynamic hyperinflation in COPD phenotypes has not been studied.MethodsWe studied moderate to severe COPD patients with varying extent of emphysema as evaluated by high-resolution thin-section lung CT. Spirometry including inspiratory capacity (IC) was measured before and immediately after metronome paced hyperventilation (MPH) at 2 times resting respiratory rate for 20 s to induce dynamic hyperinflation. Spirometry was obtained at baseline and pre- and 1.5 h post-18 μg tiotropium via HandiHaler after 30 day tiotropium treatment period in a single blind, open label intervention.ResultsIn 29 COPD patients (15 M), age 70 ± 9 years (mean ± SD) with smoking history of 53 ± 37 pack years, baseline forced expiratory volume in 1 s (FEV₁) post-180 μg albuterol MDI was 1.6 ± 0.4 L (61 ± 8% predicted) and FEV₁/FVC 59 ± 6%. Lung CT emphysema score (LCTES) was 23 ± 20 (mean ± SD) on a scale of 0–100 (none to most severe emphysema). After 30-day tiotropium, FEV₁ increased 101 ± 124 mL (mean ± SD) (p < 0.001) and Spearman correlation (r) = ?0.04, p = 0.8 with LCTES; IC increased 163 ± 232 mL (p < 0.001), and r = ?0.2, p = 0.3 with LCTES. Results following MPH induced DH before and after 30-day tiotropium were significant (p < 0.001) and similar: IC decreased 340 ± 280 mL before and 337 ± 270 mL after tiotropium, and r = ?0.3, p = 0.9 with LCTES.ConclusionTiotropium significantly increased FEV₁ (L) and inspiratory capacity in moderate-severe COPD, independent of extent of lung CT emphysema score. Despite bronchodilation and lower resting lung volume, tiotropium did not abbreviate induced dynamic hyperinflation, which was also independent of underlying emphysema.     

The efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis

BackgroundLymphangioleiomyomatosis (LAM) is a rare disease caused by dysregulated activation of the mammalian target of rapamycin (mTOR). Sirolimus, an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas and stabilize pulmonary function in patients with LAM. However, the optimal dose for the treatment of LAM remains unclear.MethodsWe conducted a retrospective, observational study of 15 patients with LAM who underwent sirolimus therapy for more than 6 months. The efficacy was evaluated by reviewing the patients' clinical courses, pulmonary function and chest radiologic findings before and after the initiation of sirolimus treatment.ResultsAll patients had blood trough levels of sirolimus lower than 5 ng/mL. Sirolimus treatment improved the annual rates of change in FVC and FEV₁ in the 9 patients who were free from chylous effusion (FVC, ?101.0 vs. +190.0 mL/y, p=0.046 and FEV₁, ?115.4 vs. +127.8 mL/y, p=0.015). The remaining 7 patients had chylous effusion at the start of sirolimus treatment; the chylothorax resolved completely within 1?5 months of treatment in 6 of these cases. These results resembled those of previous studies in which blood trough levels of sirolimus ranged from 5 to 15 ng/mL.ConclusionsLow-dose sirolimus (trough level, 5 ng/mL or less) performed as well as the higher doses used previously for improving pulmonary function and decreasing chylous effusion in patients with LAM.     

Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist,in COPD patients

NVA237 is a novel once-daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and bronchodilator efficacy of two doses of NVA237 (100 and 200 μg), versus placebo, in patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV₁] ≥ 30% and <80% predicted and FEV₁/forced vital capacity [FVC] < 0.7, 30 min after inhalation of 80 μg ipratropium bromide). After appropriate washout periods, patients were randomized to treatment with NVA237 100 μg (n = 92), NVA237 200 μg (n = 98) or placebo (n = 91) for 28 days. The primary objective was evaluation of safety, with efficacy measures included as secondary objectives. NVA237 was generally well tolerated and associated with a frequency and distribution of adverse events similar to placebo. Serious adverse events were uncommon and there was no evidence of adverse cardiovascular effects or unexpected events. Trough FEV₁ was significantly higher in those receiving NVA237 compared with placebo. For NVA237 100 μg the differences were 131 and 161 mL on Days 1 and 28, respectively (p < 0.05), and for NVA237 200 μg the differences were 146 and 151 mL on Days 1 and 28, respectively (p < 0.05). Peak FEV₁, FEV₁ at all timepoints up to 24 h after dosing, and FEV₁ area under the curve during 5 min–5 h post-dosing were also significantly higher in both NVA237 groups, compared with placebo. Patients receiving NVA237 required fewer daily puffs of rescue medication and had a higher percentage of days on which rescue medication was not required. Overall, the present study provides further evidence of the safety, tolerability and bronchodilator efficacy of once-daily treatment with NVA237 100 and 200 μg in patients with moderate-to-severe COPD.     

Bronchodilator effects of indacaterol and formoterol in patients with COPD

BackgroundResting inspiratory capacity (IC) reflects static hyperinflation in chronic obstructive pulmonary disease (COPD). This study compared the effects of formoterol and indacaterol, a novel once-daily ultra-long-acting β₂-agonist (or ultra-LABA), on resting IC and forced expiratory volume in 1 s (FEV₁).MethodsThirty patients with COPD (mean FEV₁/FVC 0.49, mean FEV₁ 56% predicted) each inhaled three treatments (two in randomized sequence followed by open-label formoterol) on separate study days: a single dose of indacaterol 300 μg, matching placebo, and two doses of formoterol 12 μg 12 h apart.ResultsIndacaterol and formoterol increased FEV₁ and IC at all time points relative to placebo (p < 0.001). Peak effects on FEV₁ were similar, while indacaterol had a greater effect on peak IC (31% vs 23% from pre-dose; p = 0.034). Indacaterol had a greater effect than formoterol on FEV₁ at 8 h (1.47 vs 1.39 L; p = 0.014) and 24 h (1.44 vs 1.35 L; p = 0.003), and on IC from 4 to 24 h (differences of 0.13–0.19 L; p < 0.05). At 24 h, indacaterol and formoterol increased FEV₁ by 17.7% and 7.5%, respectively, from pre-dose.ConclusionsThis study discriminated between the effects on IC and FEV₁ of once daily indacaterol and twice daily formoterol. The greater effect of indacaterol on IC may translate into improved long-term clinical outcomes.     

Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department

RationaleTreatment of severe asthma may be difficult despite the use of several medications including parenteral corticosteroids. Intravenous magnesium sulfate (MgSO₄) is one ancillary drug for severe crisis; its inhaled use is controversial.ObjectivesTo evaluate the usefulness of inhaled MgSO₄ compared to placebo in improving lung function, oxygen saturation, and reducing hospital admission as an adjunct to standard treatment in severe asthma crisis.Patients and methodsWe conducted a placebo-controlled, double-blind clinical trial with asthmatic patients >18 years of age with asthmatic crisis and FEV₁ < 60% of predicted (%p). All subjects received 125 mg of IV methylprednisolone followed by nebulization with the combination of albuterol (7.5 mg) and ipratropium bromide (1.5 mg) diluted in 3 ml of isotonic saline solution (as placebo) or 3 ml (333 mg) of MgSO₄. After 90 min, subjects with FEV₁ < 60%p or SpO₂ < 88% or persistent symptoms were admitted to the emergency department (ED).ResultsWe included 30 patients per group who were similar at baseline. The MgSO₄ group showed higher post-bronchodilator (post-BD) FEV₁%p (69 ± 13 vs. 61 ± 12, p < 0.014) and SpO₂ (92 ± 4 vs. 88 ± 5%, p < 0.006) than the placebo group. Fewer treated patients were admitted to the ED (5 vs. 13) (p < 0.047), with relative risk (RR) of 0.26 (95% CI 0.079–0.870).ConclusionsAdding inhaled MgSO₄ treatment to standard therapy in severe asthma crisis improves FEV₁%p and SpO₂ post-BD and reduces the rate of ED admissions.     

Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis

BackgroundThymus and activation-regulated chemokine (TARC), a member of the CC chemokine family, plays a crucial role in Th2-specific inflammation. We aimed to determine the concentration of sputum TARC in children with asthma and eosinophilic bronchitis (EB) and its relation with eosinophilic inflammation, pulmonary function, and bronchial hyper-responsiveness.MethodsIn total, 90 children with asthma, 38 with EB, and 45 control subjects were enrolled. TARC levels were measured in sputum supernatants using an ELISA. We performed pulmonary function tests and measured exhaled fractional nitric oxide, eosinophil counts in blood, and sputum and serum levels of total IgE in all children.ResultsSputum TARC levels were significantly higher in children with asthma than in either children with EB (p = 0.004) or the control subjects (p = 0.014). Among patients with asthma, sputum TARC concentration was higher in children with sputum eosinophilia than in those without sputum eosinophilia (p = 0.035). Sputum TARC levels positively correlated with eosinophil counts in sputum, serum total IgE levels, exhaled fractional nitric, and the bronchodilator response. Negative significant correlations were found between sputum TARC and FEV1/FVC (the ratio of forced expiratory volume in one second and forced expiratory vital capacity) or PC₂₀ (the provocative concentration of methacholine causing a 20% decrease in the FEV₁).ConclusionElevated TARC levels in sputum were detected in children with asthma but not in children with EB. Sputum TARC could be a supportive marker for discrimination of asthma from EB in children showing characteristics of eosinophilic airway inflammation.     

Role of add-on zileuton on total exhaled, large airway, and small airway/alveolar nitric oxide in moderate-severe persistent adult asthmatics on fluticasone 250 μg/Salmeterol 50 μg

BackgroundMeasuring non-invasive exhaled biomarkers of inflammation may be important in monitoring asthma therapy.ObjectiveEvaluate exhaled nitric oxide with add-on leukotriene synthesis inhibitor in moderate-severe persistent asthmatics on combination controllers.MethodsIn a non-randomized, non-placebo, single-blind, fixed sequence, pilot study, we evaluated 22 non-smoking, stable, moderate-severe adult asthmatics on maintenance inhaled fluticasone 250 μg/salmeterol 50 μg (F/S) via MDI bid ≥ 1 yr, with add-on oral zileuton 600 mg qid. Exhaled fractional nitric oxide (FENO) gas exchange, large airway NO, small airway/alveolar NO concentration (CANO), Juniper score and lung function were measured. Asthmatics were studied at baseline only on F/S bid (visit 1), on F/S bid pre and 2 h post first dose zileuton 600 mg (visit 2), and post 4 weeks (visit 3) F/S bid plus zileuton 600 mg qid. Values were compared at each visit and to healthy non-smoking age matched healthy controls with normal lung function.ResultsThree asthmatics stopped zileuton prematurely (headache and/or nausea) and 19 (12F) age 55 ± 17 yr (mean ± SD) completed the 4-week study. Baseline forced expiratory lung volume in 1 sec (FEV₁) was 1.6 ± 0.7L (53 ± 19% pred) (mean ± SD), FEV₁ over FVC ratio was 64 ± 11% and post 180 μg albuterol FEV₁ was 1.8 ± 0.7 L (56 ± 21% pred), and FEV₁ over FVC ratio was 67 ± 12%. Baseline Juniper scores were mild (10 ± 10) and similar (p = ns) at all visits. Baseline FENO@50 mL/s was 48 ± 27 ppb (mean ± SD), and FENO@100 mL/s was 29 ± 16 ppb, and were similar (p = ns) at all visits. Large airway NO flux was 2.0 ± 1.3 nL/s (52% asthmatics abnormal) and small airway/alveolar NO was 8.0 ± 4.0 ppb (79% asthmatics abnormal) and were similar (p = ns) at all visits. Compared to baseline, post 26 ± 6 days Zileuton, mean FEV₁ (L)% predicted increased 3.3% predicted (p = 0.03), and FEV₁ over FVC ratio increased 2.2% (p = 0.03).ConclusionIn stable, moderate-severe persistent adult asthmatics, large airway NO flux, small airway/alveolar CANO, and Juniper airway scores, were not significantly different on F/S bid vs F/S bid plus Zileuton for 4 weeks, despite significant small increase in FEV₁ over FVC ratio and FEV₁% predicted.     

Effect of interferon-α on pulmonary function and airway responsiveness in patients with chronic hepatitis C

BackgroundInterferon (IFN)-α is the only approved treatment for chronic hepatitis C. Interstitial pneumonia and, rarely, exacerbation of bronchial asthma have been reported as adverse pulmonary effects of IFN-α treatment. The purpose of the present study was to clarify whether IFN-α treatment affects pulmonary function and airway responsiveness in patients with chronic hepatitis C.MethodsWe studied 17 patients (nine males and eight females; mean age 46 years; range 30–62 years) with chronic active hepatitis C diagnosed by serum tests and liver biopsy. Pulmonary function tests included vital capacity (VC), forced expiratory volume in 1 s (FEV₁), forced expiratory flow in the middle half of the forced vital capacity (FVC_25–75%), total lung capacity and carbon monoxide diffusing capacity of the lung (D_LCO), which was adjusted for hemoglobin concentration. Airway responsiveness was measured by methacholine inhalation challenge and determination of the provocative concentration of methacholine causing a 20% fall in FEV₁ (PC₂₀). These tests were performed before and 3 months after initiation of IFN-α therapy.ResultsNo patient developed interstitial pneumonia, although there was a tendency for the hemoglobin-adjusted D_LCO to decrease. Other pulmonary function test parameters were not affected. Overall, there was no significant change in PC₂₀ (from 15.0 to 11.4 mg/mL). In three patients whose initial PC₂₀ was within the normal range, airway hyperresponsiveness was induced and one patient developed bronchial asthma after IFN-α therapy.ConclusionsThese findings suggest that IFN-α induces airway hyperresponsiveness to methacholine in a few patients with chronic hepatitis C.     

Interstitial lung disease related to rheumatoid arthritis: Evolution after treatment

ObjectiveTo describe the evolution of lung function in a cohort of rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) treated according to the medical judgment of attending physicians.MethodsRetrospective cohort of RA patients with ILD, defined by a restrictive pattern in lung function tests and evidence of ILD in high resolution computed tomography (HRCT). Patients had an assessment of lung function including spirometry, diffusing capacity for carbon monoxide (DLCO), and HRCT. At a minimum of 4 months of follow up, a second assessment of lung function was done. All patients received a high dose of prednisone (1 mg/kg/day) scheme for 6 weeks with a reduction scheme ending with a dose of 10 mg/day of prednisone at about 6–8 months of follow up. Methotrexate was used in 18/40 (45%) patients and leflunomide or azathioprine or both were indicated in 22/40 (55%).ResultsForty patients were identified. An indeterminate pattern with diffuse ground glass and reticulation images (50%) was the most prevalent pattern on HRCT scans. At a minimum of 4 months of follow up, an improvement in basal FVC values was observed (median (IQR)) 1.47 Lts. (0.99–1.91) vs 1.66 Lts. (1.37–2.1)), P < 0.004. Patients with lower Kazerooni scores for fibrosis (<0.47) had a better improvement in the FVC values.ConclusionsPatients with RA and ILD may have an improvement in the FVC after a treatment with high doses of corticosteroids and disease modifying antirheumatic drugs (DMARDs).