Susana Gómez-Ollés

Effects of salbutamol on exhaled breath condensate biomarkers in acute lung injury: prospective analysis

IntroductionThe benefits of β-adrenergic stimulation have been described in acute lung injury (ALI), but there is still no evidence of its anti-inflammatory effect in these patients. Biomarkers in exhaled breath condensate (EBC) were used to study the effects of salbutamol on lung inflammation in mechanically ventilated patients with ALI.MethodsEBC was collected before and 30 minutes after administration of inhaled salbutamol (800 μg). The following parameters were measured in the samples: volume obtained, conductivity, pH after helium deaeration, and concentration of nitrites, nitrates and 8-isoprostane. The leukotriene B4 concentration was measured after sample lyophilization and reconstitution. Results are expressed as the median (interquartile range).ResultsEBC was obtained from six ALI patients, with a median age of 56 (46 to 76) years. At the time of EBC collection, the Lung Injury Score was 3 (2.3 to 3.1) and the PaO2/FIO2 ratio was 133 (96 to 211) mmHg. A significant increase in deaerated EBC pH was observed after salbutamol administration (7.66 (7.58 to 7.75) versus 7.83 (7.67 to 7.91), P = 0.028). Trends toward decreased nitrosative species (18.81 (13.33 to 49.44) μM versus 21.21 (8.07 to 29.83) μM, P = 0.173) and decreased 8-isoprostane concentration (11.64 (7.17 to 17.13) pg/ml versus 6.55 (4.03 to 9.99) pg/ml, P = 0.068) were detected. No changes in leukotriene B4 concentration were found (1.58 (0.47 to 3.57) pg/ml versus 2.06 (1.01 to 3.01) pg/ml, P = 0.753).ConclusionEBC analysis is a noninvasive technique that can be used to monitor ventilated patients. In EBC from a small cohort of patients with ALI, inhaled salbutamol significantly decreased airspace acidosis, a marker of inflammation, and was associated with a trend toward decreased markers of nitrosative and oxidative stress.

Evolución de la hiperrespuesta bronquial en pacientes con asma ocupacional por exposición a sales de persulfato

Objetivo: Las sales de persulfato son uno de los agentes m?s frecuentemente implicados en el origen del asma ocupacional (AO). El objetivo de este estudio ha sido establecer la evoluci?n de la hiperrespuesta bronquial y de las pruebas inmunol?gicas en pacientes con AO por persulfatos en funci?n de que persista o no la exposici?n a dichas sales. Pacientes y m?todos: Se estudi? a 10 pacientes con AO por exposici?n a sales de persulfato, diagnosticados con prueba de provocaci?n bronquial espec?fica, en los que como m?nimo hab?an transcurrido 3 a?os tras el diagn?stico. En todos los casos se realizaron un exhaustivo interrogatorio cl?nico y laboral, espirometr?a forzada y prueba de provocaci?n bronquial inespec?fica con metacolina, se determinaron los valores de inmunoglobulina E total y se practicaron pruebas cut?neas con las distintas sales de persulfato. Resultados: En el momento del control evolutivo, 7 pacientes hab?an abandonado la exposici?n a persulfatos. De los pacientes con hiperrespuesta bronquial positiva que hab?an abandonado el trabajo, se observ? una mejor?a significativa de ?sta en 3 de ellos. Este hecho no se observ? en ninguno de los pacientes que siguieron expuestos. La prueba cut?nea espec?fica se negativiz? en 3 pacientes que no estaban expuestos en el momento del control evolutivo. Desde el punto de vista cl?nico, la mayor?a de los pacientes continuaron presentando s?ntomas, aunque ?stos hab?an mejorado, excepto en un caso en que, a pesar de evitar la exposici?n, empeoraron. Conclusiones: Aunque pueden persistir los s?ntomas de asma y la hiperrespuesta bronquial positiva, la evoluci?n de los pacientes con AO por persulfato parece ser favorable si se evita la exposici?n. Esta respuesta no parece diferir de la comunicada en otros casos de AO.

Mechanical ventilation induces changes in exhaled breath condensate of patients without lung injury

INTRODUCTION Measurement of biomarkers in exhaled breath condensate (EBC) may be useful for monitoring lung inflammation and injury in mechanically ventilated patients. The aim of this study was to analyze changes in biomarkers of inflammation in EBC associated with prolonged mechanical ventilation. METHODS EBC samples were collected from critically ill patients weaning from mechanical ventilation without lung disease and from healthy nonsmokers. The following parameters were measured: pH after helium deaeration, nitrogen oxide and 8-isoprostane concentrations. RESULTS EBC was obtained from 10 patients and 20 controls. Ventilation time before the start of sample collection was 250 (85-714)h. The post-deaeration pH of EBC samples was significantly lower in ventilated patients than controls (7.50 [7.28-7.70] vs 8.07 [7.60-8.40]; P=0.008). Ventilation time before sample collection inversely correlated with pH (r=-0.636; P=0.048). A significantly higher concentration of nitrogen oxide (muM) was seen in ventilated patients vs controls (66.22 [22.26-83.13] vs 15.06 [10.73-23.30]; P=0.002), whereas levels of 8-isoprostane (pg/mL) were not significantly different between both groups (5.73 [4.0-11.4] vs 9.09 [6.63-11.43]; P=0.169). The nitrogen oxide concentration correlated negatively with dynamic compliance (r=-0.952; P<0.001) and positively with respiratory rate (r=0.683; P=0.029). CONCLUSIONS EBC analysis is a non-invasive technique that can be used to monitor ventilated patients. Mechanically ventilated patients had higher EBC acidity and nitrogen oxide concentrations. Duration of ventilation correlated with breath condensate pH.

Course of Bronchial Hyperresponsiveness in Patients With Occupational Asthma Caused by Exposure to Persulfate Salts

OBJECTIVE Persulfate salts are among the most frequently implicated causes of occupational asthma. The aim of this study was to describe the course of bronchial hyperresponsiveness and immunologic test results in patients with occupational asthma due to persulfate salts. PATIENTS AND METHODS Ten patients with occupational asthma due to persulfate salts were studied. Diagnosis was based on specific bronchial challenge tests performed at least 3 years before enrollment. An exhaustive medical and work history was taken during interviews with all patients, and all underwent spirometry and nonspecific bronchial challenge testing. Total immunoglobulin E levels were determined and skin prick tests to several persulfate salts were performed. RESULTS At the time of evaluation, 7 patients had avoided workplace exposure to persulfate salts. The bronchial hyperresponsiveness of 3 of those 7 patients had improved significantly. No improvement was observed in patients who continued to be exposed. Specific skin prick tests became negative in 3 patients who were no longer exposed at the time of the follow-up evaluation. Most of the patients continued to report symptoms, although improvements were noted. One patient, however, reported worsening of symptoms in spite of avoidance of exposure. CONCLUSIONS Although asthma symptoms and bronchial hyperresponsiveness may persist for patients with occupational asthma due to persulfate salts, their condition seems to improve if they avoid exposure. This course does not seem to differ from that reported for other cases of occupational asthma.

An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe

Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies. 13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway. After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000–1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200–1000 and 100–500 m, respectively (hazard ratio 1.085– 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations. Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides. Long-term residential air pollution/traffic exposure associated with CLAD and survival after lung transplantation http://ow.ly/Izxj304uA5k

Occupational Asthma Due to Colistin in a Pharmaceutical Worker

To our knowledge, this is the first case report of a 24-year-old man working in a pharmaceutical company transporting and storing raw materials who developed occupational asthma (OA) to colistin. The specific inhalation challenge confirmed the diagnosis of OA to colistin. Specific IgE was not detected, because dot-blot analysis was negative at all colistin concentrations tested. To our knowledge, OA due to a peptide antibiotic has not previously been described. This antibiotic should be listed as a trigger of OA.

Sputum Inflammatory Profile Before and After Specific Inhalation Challenge in Individuals with Suspected Occupational Asthma

Background The aim of this study was to establish the sputum inflammatory profile and changes in levels of leukotriene B4 (LTB4) and a panel of Th1/Th2 cytokines in subjects with suspected occupational asthma (OA) following specific inhalation challenge (SIC) to high-molecular-weight (HMW) and low-molecular-weight (LMW) agents. Material and Methods Fifty-one consecutive subjects undergoing SIC for suspected OA were enrolled. Sputum induction was performed the day before and 24 h after exposure to the offending agent. Total and differential cell counts were assessed. LTB4 and a 10 Th1/Th2 cytokines were measured in sputum supernatant. Results Thirty-four patients tested positive to SIC and were diagnosed with OA (in 10 due to HMW agents and in 24 to LMW agents). SIC was negative in 17 subjects. As compared to baseline an increase was found in the percentage of sputum eosinophils and neutrophils, and in IL-10 concentration after SIC (p = 0.0078, p = 0.0195, and p = 0.046, respectively), and a decrease was seen in LTB4 level (p = 0.0078) in patients with OA due to HMW agents. An increase in the percentage of sputum neutrophils after SIC (p = 0.0040) was observed in subjects without OA exposed to LMW agents. IL-8 levels after SIC were higher in patients without OA compared with patients with OA (p = 0.0146). Conclusion When conducting airway inflammation studies in OA, patients should be divided according to the causal agent (HMW or LMW). In OA patients exposed to HMW agents, an increase in the number of neutrophils can be found in parallel to the increase of eosinophils, although this does not contradict an IgE-mediated mechanism. Exposure to LMW agents can result in increased neutrophilic inflammation in patients with airway diseases unrelated to OA. There is variability in the responses observed in patients with OA exposed to LMW agents.

Diagnostic utility of exhaled breath condensate analysis in conjunction with specific inhalation challenge in individuals with suspected work-related asthma

BACKGROUND Establishing the role of exhaled breath condensate (EBC) analysis in work-related asthma (WRA), and more specifically, in conjunction with specific inhalation challenge (SIC), is difficult. OBJECTIVE To measure EBC pH, and nitrite/nitrate concentrations before and after SIC in individuals with suspected WRA exposed to either high-molecular-weight (HMW) or low-molecular-weight (LMW) agents and evaluate whether these changes are useful to distinguish between occupational asthma (OA) and work-exacerbated asthma (WEA). METHODS One hundred twenty-five consecutive workers undergoing SIC were enrolled. Exhaled breath condensate was collected at the end of the baseline day and 24 hours after exposure to the offending agent. In all EBC samples, pH was measured, and nitrite and nitrate concentrations were determined. RESULTS Specific inhalation challenge was positive in 66 individuals, who were then diagnosed with OA. Work-exacerbated asthma was diagnosed in 14, and in 45 patients establishing a direct relationship between the symptoms and work exposure was not possible. In patients with WEA, EBC pH values after SIC were significantly lower than those before SIC (P = .0047). Using the receiver operating characteristic (ROC) curve, we found that an EBC pH decrease of greater than 0.4 units after SIC achieved the most satisfactory sensitivity 79% (confidence interval [CI]: 49-94) and specificity of 100% (CI: 68-100), considering only patients with asthma and without OA. A decrease in EBC pH of 0.4 or more common in those exposed to HMW agents (8/19, 42%) than in those exposed to LMW agents (7/47, 15%). CONCLUSIONS Exhaled breath condensate pH in conjunction with SIC may be useful for diagnosing WEA.

Bronchial inflammation in hypersensitivity pneumonitis after antigen-specific inhalation challenge

The aim of this study is to compare the inflammatory profile before and after specific inhalation challenge (SIC) in induced sputum from patients with hypersensitivity pneumonitis (HP) and to investigate whether different causal antigens define the resulting profile.

Occupational Asthma Related to Mouse Allergen Exposure and Rhinoconjunctivitis due to Collagenase Inhalation in a Laboratory Technician

We describe the case of a 27-year-old patient working in a research laboratory, who developed occupational asthma to mouse proteins and presented symptoms of rhinoconjunctivitis caused by manipulation of collagenase. Specific inhalation challenge confirmed the diagnosis of occupational asthma to mouse proteins, whereas specific challenge with collagenase only evoked symptoms of rhinitis and conjunctivitis. SDS-PAGE and Western blot analysis for collagenase showed that the patient’s IgE antibodies bound specifically to a protein with a molecular weight of 92 kDa. Hence, this was an unusual case of double sensitization. The sensitization to collagenase presented in this report may represent a new occupational disease in technicians working in medical or research laboratories.