RESUMO
To determine seasonal variability in mineralization dynamics of mussel biodeposits, we applied a multiple-element approach measuring mineralization rates of carbon (C), nitrogen (N), phosphorus (P) and silicate (Si) during three periods (March, August and November). The results of this study showed that mineralization rates vary between seasons and between elements and that mineralization dynamics were influenced by both temperature and biodeposit nutrient composition. Mineralization rates were 3.2 ± 0.4 mmol C, 0.17 ± 0.04 mmol N, 0.06 ± 0.02 mmol P and 3.91 ± 3.75 mmol Si per gram biodeposit (DW) per day, which represented 24 % of the particulate organic C and 17 % of the particulate organic N in mussel biodeposits. Seasonal variability was largest for Si mineralization with 60-80-fold higher rates measured in March compared to August and November. This difference is most likely related to the difference in biodeposit nutrient composition. It was furthermore shown that the labile fraction of biodeposits became mineralized after, respectively, 18, 9 and 13 days during the experimental periods in March, August and November. This indicates that temperature enhances biodeposit decomposition with approximately 2-3 times faster turnover at a 10 °C temperature interval (Q10 ).
RESUMO
Sputum colour is regarded as a good marker of bacterial involvement in acute exacerbations of chronic obstructive pulmonary disease (COPD) and guides many physicians in deciding on antibiotic treatment. Although most doctors rely on the sputum colour that is reported by patients, it can also be assessed using a validated colour chart. In this study, reported sputum colour and assessed sputum colour were compared as markers of the presence of bacteria, bacterial load, and systemic inflammation. Data on 257 exacerbations in 216 patients hospitalized with an acute exacerbation were analysed (mean age, 72 years; mean forced expiratory volume in 1 s, 44.8% + or - 17.8% (+ or - standard deviation)). Sputum colour was reported by the patients and assessed at the laboratory with a colour chart. Subsequently, quantitative sputum cultures were performed. C-reactive protein was measured as a marker of systemic inflammation. A sputum sample was obtained in 216 exacerbations (84%), of which 177 (82%) were representative. A pathogen was identified in 155 patients (60%). Assessed sputum colour was a better marker of the presence of bacteria (OR 9.8; 95% CI 4.7-20.4; p <0.001) than reported sputum colour (OR 1.7; 95% CI 1.0-3.0; p 0.041). The sensitivity and specificity were 73% and 39% for reported sputum colour, and 90% and 52% for assessed sputum colour. Assessed sputum colour was clearly related to sputum bacterial load and C-reactive protein levels, whereas reported sputum colour was not. It is concluded that sputum colour reported by patients is an unreliable marker of the presence of bacteria in acute exacerbations of COPD. Assessed sputum colour is clearly superior and is also related to bacterial load and systemic inflammation.
Assuntos
Biomarcadores , Cor , Anamnese/métodos , Pneumonia Bacteriana/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Escarro , Idoso , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Técnicas Bacteriológicas/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/patologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Sensibilidade e EspecificidadeRESUMO
A beneficial effect of long-term corticosteroid treatment in patients with COPD may be linked to suppressing inflammation, in particular neutrophilic inflammation. Effects on neutrophilic and eosinophilic inflammation and on lung function of long-term inhaled budesonide treatment (800 microg daily, 6 months, double-blind, randomised, cross-over versus placebo) were studied and compared to the effects of 3 weeks oral prednisolone (30 mg daily) in 19 patients with COPD (mean age 63 y, FEV(1) 65% of predicted). Neither treatment influenced neutrophilic inflammation. Inhaled budesonide compared to placebo significantly reduced sputum % eosinophils at 3 months (-42%, p = 0.036), but not significantly at 6 months (-31%, p = 0.78). Eosinophil count per g sputum was decreased with 30% at 3 months (p = 0.09) and with 9% at 6 months (p = 0.78). FEV(1) was slightly higher after 6 months budesonide (+2.5% predicted, p = 0.09). Prednisolone significantly reduced sputum % eosinophils (-87%, p = 0.007), but did not affect eosinophil count per g sputum and did not improve FEV(1) (-0.6% predicted, p = 0.40). A higher baseline FEV(1) (%) correlated with effects of budesonide on FEV(1) (p < 0.001), effects on sputum interleukin-8 and eosinophil cationic protein (both p < 0.05) and tended to correlate with effects on sputum % eosinophils (p = 0.056). Baseline inflammatory data and effects of prednisolone did not correlate with effects of budesonide. Effects of inhaled budesonide in COPD are not restricted to patients with severe disease and may be linked to a suppression of eosinophilic inflammation. Investigating effects of prednisolone has no predictive value for long-term treatment.
Assuntos
Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Glucocorticoides/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Administração Oral , Idoso , Estudos Cross-Over , Método Duplo-Cego , Eosinófilos/patologia , Feminino , Volume Expiratório Forçado , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Prednisolona/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Escarro/citologiaRESUMO
We describe three patients with progressive fibrosing interstitial lung disease (ILD) as the first and only manifestation of systemic sclerosis. In one patient the presence of anti-Scl-70 autoantibodies suggested systemic sclerosis to be the underlying cause of the disease. In the two other subjects, however, anti-Scl-70 antibodies were negative. In these patients the lung disease preceded other manifestations of systemic sclerosis by several years. Diagnosis, prognosis and treatment of systemic sclerosisassociated ILD is discussed.
Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Adulto , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnósticoRESUMO
Toll-like receptors (TLRs) are pattern-recognition receptors that have been implicated in the initiation of innate immune responses upon the first encounter with invading pathogens. The airways are frequently exposed to various types of lipopolysaccharide (LPS) from the environment or from pathogens. The current study was designed to determine the effect of LPS on TLR gene expression in human alveolar macrophages in vivo. In total, 16 healthy subjects were enrolled in a single-blinded, placebo-controlled study. Subjects inhaled 100 microg LPS or normal saline (n = 8 per group). Measurements were performed in alveolar macrophages purified from bronchoalveolar lavage fluid obtained 6 h post-challenge. Inhalation of LPS by healthy human volunteers resulted in enhanced alveolar macrophage expression of mRNAs encoding TLRs 1, 2, 7, 8 and CD14, and reduced expression of mRNAs encoding TLR4 and lymphocyte antigen 96. In conclusion, lipopolysaccharide differentially influences the toll-like receptor mRNA expression profile in human alveolar macrophages in vivo.
Assuntos
Endotoxinas/toxicidade , Expressão Gênica , Lipopolissacarídeos/toxicidade , Macrófagos Alveolares/imunologia , Receptores Toll-Like/genética , Administração por Inalação , Adulto , Endotoxinas/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Lipopolissacarídeos/administração & dosagem , Macrófagos Alveolares/efeitos dos fármacos , Masculino , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Receptores Toll-Like/efeitos dos fármacosRESUMO
BACKGROUND: Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma. METHODS: After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period. RESULTS: Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001). CONCLUSIONS: The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.
Assuntos
Albuterol/análogos & derivados , Androstadienos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Bronquite/tratamento farmacológico , Broncodilatadores/administração & dosagem , Administração por Inalação , Adulto , Albuterol/administração & dosagem , Análise de Variância , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Fluticasona , Humanos , Masculino , Pessoa de Meia-Idade , Xinafoato de Salmeterol , Resultado do TratamentoRESUMO
BACKGROUND: There is much controversy about the ideal approach to the management of community acquired pneumonia (CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. METHODS: In a prospective randomised open study performed between 1998 and 2000, a pathogen directed treatment (PDT) approach was compared with an empirical broad spectrum antibiotic treatment (EAT) strategy according to the ATS guidelines of 1993 in 262 hospitalised patients with CAP. Clinical efficacy was primarily determined by the length of hospital stay (LOS). Secondary outcome parameters for clinical efficacy were assessment of therapeutic failure on antibiotics, 30 day mortality, duration of antibiotic treatment, resolution of fever, side effects, and quality of life. RESULTS: Three hundred and three patients were enrolled in the study; 41 were excluded, leaving 262 with results available for analysis. No significant differences were found between the two treatment groups in LOS, 30 day mortality, clinical failure, or resolution of fever. Side effects, although they did not have a significant influence on the outcome parameters, occurred more frequently in patients in the EAT group than in those in the PDT group (60% v 17%, 95% CI -0.5 to -0.3; p<0.001). CONCLUSIONS: An EAT strategy with broad spectrum antibiotics for the management of hospitalised patients with CAP has comparable clinical efficacy to a PDT approach.
Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Adulto , Idoso , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Mortalidade Hospitalar , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Pneumonia Bacteriana/mortalidade , Estudos Prospectivos , Resultado do TratamentoRESUMO
In a prospective study to evaluate the diagnostic yield of different microbiological tests in hospitalised patients with community-acquired pneumonia, material for microbiological investigation was obtained from 262 patients. Clinical samples consisted of the following: sputum for Gram staining, culture, and detection of pneumococcal antigen; blood for culture and serological tests; urine for detection of Legionella pneumophila serogroup 1 antigen and pneumococcal antigen; and specimens obtained by fiberoptic bronchoscopy. A pathogen was identified in 158 (60%) patients, with Streptococcus pneumoniae (n=97) being the most common causative agent of community-acquired pneumonia. In 82% of the 44 patients with an adequate sputum specimen, a positive Gram stain was confirmed by positive sputum culture. S. pneumoniae infections were detected principally when adequate sputum specimens were examined by Gram stain and culture and when adequate and inadequate sputum specimens were tested for the presence of pneumococcal antigen (n=58; 60%). The urinary pneumococcal antigen test was the most valuable single test for detection of S. pneumoniae infections (n=52; 54%) when sputum pneumococcal antigen determination was not performed. Fiberoptic bronchoscopy was of additive diagnostic value in 49% of the patients who did not expectorate sputum and in 52% of those in whom treatment failed. Investigation of sputum by a combination of Gram stain, culture, and detection of pneumococcal antigen was the most useful means of establishing an aetiological diagnosis of community-acquired pneumonia, followed by testing of urine for pneumococcal antigen. Fiberoptic bronchoscopy may be of additional value when treatment failure occurs.
Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Feminino , Humanos , Masculino , Técnicas Microbiológicas , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
The aim of the present study was to investigate whether the pneumonia severity index (PSI) could adequately predict the severity of community-acquired pneumonia (CAP) and could be used as a severity of illness classification system. Furthermore, reasons that may influence the decision to admit low risk patients were analysed. In a prospective study 260 patients with CAP were included. Stratification in five risk classes according to the PSI was compared with parameters that are closely related to severity of CAR A significant difference in severity parameters, such as length of stay (P < 0.001) and simplified acute physiologic score and acute physiologic and chronic health evaluation II score (P < 0.001) was found between the five risk classes. Furthermore, a positive British Thoracic Society (BTS) rule and modified BTS rule score was significantly more prevalent in the higher risk classes (P < 0.001). The patient population had an average 30-day mortality of 10% and a mean Intensive Care Unit (ICU) admission rate of 8%. The mortality rate and ICU admission rate significantly differed between the five risk classes (P < 0.001), in which the highest ICU admission rate (40.9%) and the highest mortality percentage (40.9%) were both found in risk class V. Several clinical factors (n = 64), such as an exacerbation of chronic obstructive pulmonary disease in 17 patients and clinical appearance of being ill in 16 patients, lack of improvement on outpatient antibiotic therapy (n = 15) and social circumstances (n = 3) were reasons that influenced the decision to hospitalise low risk patients (n = 82). The results show that the PSI adequately predicted the severity of CAP and can be used as a severity of illness classification in CAP. Clinical and social factors other than those mentioned in the PSI have to be considered when making the decision to hospitalise patients with CAP.
Assuntos
Pneumonia/classificação , Índice de Gravidade de Doença , APACHE , Distribuição por Idade , Infecções Comunitárias Adquiridas/classificação , Infecções Comunitárias Adquiridas/mortalidade , Cuidados Críticos , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/mortalidade , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Resultado do TratamentoRESUMO
Pulmonary abnormalities may persist long after the acute phase of legionnaires disease (LD). In a cohort of 122 survivors of an outbreak of LD, 57% were still experiencing an increased number of symptoms associated with dyspnea at a mean of 16 months after recovery from acute-phase LD. For 86 of these patients, additional evaluation involving high-resolution computed tomography (HRCT) of the lung revealed pulmonary abnormalities in 21 (24%); abnormal HRCT findings generally presented as discrete and multiple radiodensities. Residual pulmonary abnormalities were associated with a mean reduction of 20% in the gas transport capacity of the lung. This latter sign could not be used to explain the increased symptoms of dyspnea reported by patients. Receipt of mechanical ventilation during the acute phase of LD, delayed initiation of adequate antibiotic therapy, and chronic obstructive pulmonary disease were identified as risk factors for the persistence of lung abnormalities.
Assuntos
Doença dos Legionários/diagnóstico por imagem , Doença dos Legionários/fisiopatologia , Idoso , Dispneia/epidemiologia , Dispneia/etiologia , Feminino , Humanos , Legionella pneumophila , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Troca Gasosa Pulmonar , Radiografia , Testes de Função Respiratória , Fatores de RiscoRESUMO
BACKGROUND: There is evidence that surfactant protein (SP)-D is important in the innate, as well as in the adaptive pulmonary immune response. Serum concentrations of SP-D have been proposed as parameter of the integrity of the blood-airspace barrier in interstitial lung diseases. We hypothesized that serum SP-D concentrations are affected in allergic patients and correlate with changes in allergic airway inflammation. OBJECTIVE: To determine levels of serum SP-D in allergic patients compared with non-allergic controls. Furthermore, to investigate associations between serum SP-D concentrations on the one hand and changes in commonly used markers of bronchial inflammation in allergic airways disease on the other hand. MATERIALS AND METHODS: Fifty allergic patients were studied and bronchial allergen challenge was used as a model to increase bronchial allergic inflammation in these patients. Serum SP-D concentrations, inflammatory parameters in induced sputum and bronchial hyper-responsiveness (BHR) were determined before and after allergen challenge. Twenty-five non-allergic volunteers served as controls. RESULTS: Baseline serum SP-D was significantly higher in allergic patients as compared with controls (mean serum SP-D concentration (95% confidence interval): 62.7 (55.5, 70.0) in allergic patients vs. 49.5 (36.7, 62.3) ng/mL in non-allergic controls, P=0.006). In addition, baseline serum SP-D appeared to be an independent predictor for the magnitude of the late asthmatic response after allergen challenge. Furthermore, serum SP-D was predictive for the sputum eosinophil cationic protein concentration after allergen challenge. CONCLUSION: We propose that serum SP-D concentrations are associated with allergic bronchial inflammation and may give additional information, beside BHR and sputum eosinophils, about the degree of bronchial inflammation in allergic patients.
Assuntos
Hipersensibilidade/sangue , Proteína D Associada a Surfactante Pulmonar/sangue , Adulto , Alérgenos , Biomarcadores/sangue , Testes de Provocação Brônquica , Estudos de Casos e Controles , Proteína Catiônica de Eosinófilo/análise , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Escarro/imunologia , Fatores de TempoRESUMO
In vitro data suggest that salmeterol, contrary to formoterol, can partly antagonise the effect of short-acting beta(2)-agonist rescue medication. To explore whether this occurs in vivo, we compared the effects of increasing doses (200-3200 microg) of fenoterol on the recovery of methacholine induced bronchoconstriction as well as PD(20) methacholine in 23 asthmatic patients, during two-week treatment periods with placebo, and standard doses of salmeterol or formoterol in a double blind, double-dummy, crossover study. Salmeterol showed a slightly higher propensity for the development of bronchodilator tolerance. The recovery of methacholine induced bronchoconstriction was more complete during regular use of formoterol relative to salmeterol. During regular use of both long-acting beta(2)-agonists the bronchoprotective efficacy of fenoterol was attenuated, but this was more pronounced during salmeterol than during formoterol. The mean maximum increase in PD(20) metacholine after the highest dose of fenoterol was 3.97 DD during placebo, 2.47 DD during formoterol (p<0.001) and 1.81 DD during salmeterol treatment (p<0.001). We conclude that in asthmatic patients the efficacy of short-acting beta(2)-adrenoceptor agonists can be significantly attenuated during regular use of long-acting beta(2)-agonists. In this respect, differences were observed between salmeterol and formoterol that may represent the expression of partial antagonism by salmeterol.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/análogos & derivados , Albuterol/uso terapêutico , Asma/tratamento farmacológico , Broncoconstritores/antagonistas & inibidores , Broncodilatadores/uso terapêutico , Etanolaminas/uso terapêutico , Cloreto de Metacolina/antagonistas & inibidores , Adulto , Idoso , Broncoconstritores/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fumarato de Formoterol , Humanos , Masculino , Cloreto de Metacolina/efeitos adversos , Pessoa de Meia-Idade , Testes de Função Respiratória , Xinafoato de SalmeterolRESUMO
BACKGROUND: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non-asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen-induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms. METHODS: Bronchial allergen challenge was performed in 52 patients sensitized to house dust mite (Dermatophagoides pteronyssinus), of whom 26 had non-asthmatic rhinitis and 26 had asthma. Levels of eNO were measured before and 1 h, 1 day and 1 week after challenge. RESULTS: At baseline eNO was significantly lower in non-asthmatic rhinitis compared with asthma (geometric mean eNO (SEM): 121 (1.1) in non-asthmatic rhinitis vs 197 (1.1) nl/min in asthma, P < 0.006). However, the increase in eNO after bronchial allergen challenge in non-asthmatic rhinitis, in particular in those patients with a dual asthmatic response, significantly exceeded the increase in asthma resulting in similar levels of eNO after challenge (geometric mean eNO (SEM) at 24 h postchallenge 204 (1.1) in non-asthmatic rhinitis vs 244 (1.1)nl/min in asthma, P = 0.3). CONCLUSION: The difference in eNO between non-asthmatic rhinitis and asthma at baseline is abolished after allergen exposure due to a significantly greater increase in eNO in non-asthmatic rhinitis.
Assuntos
Asma/metabolismo , Testes de Provocação Brônquica/métodos , Broncodilatadores/farmacocinética , Óxido Nítrico/farmacocinética , Rinite Alérgica Perene/metabolismo , Administração por Inalação , Adulto , Alérgenos , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Histamina , Humanos , Masculino , Óxido Nítrico/administração & dosagem , Estudos Prospectivos , Pyroglyphidae , Rinite Alérgica Perene/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: It is presently unknown which factors determine the occurrence and persistence of asthma in house dust mite-allergic individuals. The level of allergen-specific IgE antibodies does not seem to be decisive for asthmatic symptoms. Moreover, levels of exposure to mite allergens do not seem to differ significantly between asthmatic and non-asthmatics individuals. AIM: It was hypothesized that the presence or absence of asthmatic symptoms in house dust mite-allergic patients is associated with quantitative or qualitative differences in the cellular bronchial inflammatory response during the late phase of the allergic reaction. This hypothesis was tested in the bronchial allergen challenge model. MATERIAL AND METHODS: Whole lung challenges with house dust mite extract were performed in 52 house dust mite-allergic subjects, of whom 26 had asthma and 26 had perennial rhinitis without asthmatic symptoms. Primary outcomes were parameters for bronchial inflammation in serial samples of induced sputum (cell differentials, eosinophil cationic protein (ECP), interleukin-8 (IL-8), myeloperoxydase (MPO)). In addition, lung function, non-specific bronchial hyper-responsiveness and serial blood samples (eosinophils and IL-5) were analysed. RESULTS: At baseline sputum eosinophils and ECP were similar in both groups but neutrophils and IL-8 were higher in asthmatics. The early bronchoconstriction after allergen challenge was similar in asthma and non-asthmatic rhinitis (median decrease in FEV1: asthma -31.7% vs. non-asthmatics -29.1%, P > 0.1). The late phase bronchoconstriction was significantly greater in asthma (median decrease in FEV1: asthma -27.6% vs. non-asthmatics -18.9%, P = 0.02). Induction of bronchial hyper-responsiveness was similar in both groups. Bronchial allergen challenge elicited significant increases in sputum eosinophils and ECP, which were indistinguishable for both groups (P > 0.1 and P = 0.07, respectively). In contrast, higher numbers of neutrophils persisted in asthma 24h after challenge and were accompanied by significant increases in IL-8 and MPO, which were absent in non-asthmatics (difference between groups P = 0.007 and P = 0.05, respectively). CONCLUSION: Allergen challenge inducedvery similar increases in eosinophils and ECP in induced sputum in allergic asthmatics and in allergic non-asthmatic patients. The difference in bronchial inflammation between asthma and non-asthmatic rhinitis appeared to be more closely related to indices for neutrophilic inflammation.
Assuntos
Alérgenos/efeitos adversos , Asma/etiologia , Hiper-Reatividade Brônquica/etiologia , Pyroglyphidae/imunologia , Rinite Alérgica Perene/etiologia , Adolescente , Adulto , Animais , Antígenos de Dermatophagoides/imunologia , Asma/imunologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/imunologia , Testes de Provocação Brônquica , Broncoconstrição , Poeira/imunologia , Eosinófilos/patologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Infiltração de Neutrófilos , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/fisiopatologia , Escarro/imunologiaRESUMO
A 33-year-old woman presented with a non-specific inflammation of the respiratory passages, which occurred two months after partial colectomy and sigmoidectomy for local stenosis caused by an unclassified inflammatory bowel disease. After other causes of the respiratory symptoms had been ruled out, it was concluded that these were a complication of the bowel disease. Due to the osteoporosis, the patient was given a prolonged treatment with high doses of inhaled corticosteroids instead of systemic corticosteroids. She was treated successfully.
Assuntos
Anti-Inflamatórios/administração & dosagem , Asma/etiologia , Doenças Inflamatórias Intestinais/complicações , Osteoporose/etiologia , Prednisona/administração & dosagem , Administração por Inalação , Adulto , Anti-Inflamatórios/efeitos adversos , Colectomia , Contraindicações , Relação Dose-Resposta a Droga , Feminino , Humanos , Doenças Inflamatórias Intestinais/cirurgia , Prednisona/efeitos adversos , Doenças Respiratórias/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: The models for exposure to house dust in research and clinical practice are selected with respect to their role in IgE-mediated immediate hypersensitivity. The use of isolated major allergens instead of complex allergen extracts is becoming increasingly popular as it offers some important advantages for quantitative measures in diagnosis and research. OBJECTIVE: To compare house dust mite extract and isolated mite major allergens with respect to their ability to induce early and late asthmatic responses and bronchial hyperreactivity. METHODS: Bronchial responses to house dust mite (HDM, Dermatophagoides pteronyssinus) extract and isolated major allergens from HDM (Der p 1 and Der p 2) were compared in a double-blind, randomized, cross-over study in 20 patients with mild to moderate asthma who were allergic to HDM. Allergen was titrated to a standardized early asthmatic response. Bronchial hyper-responsiveness to histamine (PC20histamine) was determined before and after allergen inhalation to assess allergen-induced bronchial hyper-responsiveness and IL-5 was measured in serum. In addition, the allergens were applied in intracutaneous skin tests and activation of basophil leucocytes and proliferation of peripheral blood mononuclear cells was tested in vitro. RESULTS: After a similar early asthmatic response (mean Deltaforced expiratory volume in 1 s (FEV1),max -29.4 (SD 7.2) vs. -33.1 (8.6) %; mean difference 3.6 (95% CI -0.9 to 8.2) %), the late asthmatic response (mean DeltaFEV1,max -45.9 (21.9) vs. -32.7 (22.3) %; mean difference 13.2 (3.8-22.3) %), the degree of allergen-induced bronchial hyper-responsiveness (mean DeltaPC20histamine, 1.8 (1.0) vs. 1.2 (0.9) doubling dose; mean difference 0.6 (0.2-1.1) doubling dose) and serum IL-5 at 6 h were found to be significantly higher after bronchial challenge with HDM extract than after challenge with an isolated HDM major allergen. Likewise, there was an increased late skin reaction with HDM compared with isolated major allergen after a similar early skin reaction. CONCLUSION: Constituents of HDM extract, other than Der p 1 or Der p 2, with no significant influence on the IgE-mediated early asthmatic response contribute significantly to the allergen-induced late asthmatic response and bronchial hyper-reactivity.
Assuntos
Asma/etiologia , Glicoproteínas/efeitos adversos , Extratos de Tecidos/efeitos adversos , Adolescente , Adulto , Alérgenos/efeitos adversos , Animais , Antígenos de Dermatophagoides , Asma/imunologia , Basófilos/metabolismo , Estudos Cross-Over , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Poeira/efeitos adversos , Feminino , Volume Expiratório Forçado/fisiologia , Glicoproteínas/imunologia , Liberação de Histamina , Humanos , Imunoglobulina E/metabolismo , Exposição por Inalação/efeitos adversos , Interleucina-5/sangue , Masculino , Pessoa de Meia-Idade , Ácaros , Índice de Gravidade de Doença , Testes Cutâneos , Fatores de Tempo , Extratos de Tecidos/imunologiaRESUMO
Analysis of sputum as a specimen containing inflammatory indices has gained considerable interest during the last decade with focus on chronic bronchitis (CB) with or without airway obstruction, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and asthma. The nature of the specimens requires expert skill for handling them and for performing analyses. The analysis of spontaneously produced sputum has been performed less frequently than that of induced sputum. This is surprising as several studies have shown that the collection procedures and the assay methods are highly reproducible. There are several valid parameters of sputum analysis that can be applied in research on airway inflammation and in monitoring therapy of patients. Spontaneously produced sputum can be obtained in a simple and non-invasive way, which warrants further efforts to expand the range of applications of its analysis. Here, we will critically review the procedures for collecting spontaneously produced sputum, for handling the samples, and the requirements for assay of sputum components. This will imply the reproducibility of the analysis, the recovery of solutes, the validity of assays in terms of reproducibility and of linearity of the response, the validity of the assays with respect to association with other inflammatory parameters and with clinical parameters, and the usefulness of assays with respect to their response upon treatment of patients.
Assuntos
Pneumopatias Obstrutivas/patologia , Escarro/química , Biomarcadores/análise , Contagem de Células , Citocinas/análise , Humanos , Inflamação/patologia , Reprodutibilidade dos Testes , Escarro/citologia , Escarro/enzimologiaRESUMO
The purpose of this review is to describe the present state of knowledge regarding host susceptibility factors that may determine the occurrence, development and severity of interstitial lung disease (ILD) caused by exogenous agents. First, host susceptibility may pertain to differences in the delivery and/or persistence of the noxious agent in the lung. The deposition and clearance of inhaled particles or fibres may vary depending on innate anatomical or physiological characteristics, and on acquired changes, such as nasal disease or smoking-induced alterations. Genetically- or environmentally-induced interindividual differences in the expression of pulmonary biotransformation enzymes may form the basis for, or contribute to the risk of, drug-induced interstitial lung disease. Secondly, there are genetic and acquired variations in various enzymatic and nonenzymatic defence systems that protect cells and tissues against oxidative stress, which is often involved in the pathogenesis of interstitial lung disease caused by particles, fibres, metals, organic agents and drugs. Thirdly, the occurrence of immunological sensitization is dependent on both genetic and environmental factors. This has been demonstrated in chronic beryllium lung disease and in hypersensitivity pneumonitis. Fourthly, the propensity of individuals to develop particular types of inflammation, such as granulomas, is probably under genetic control. The regulation and resolution of inflammation and fibrogenesis caused by dust particles are also partly determined by genetic factors, involving cytokine networks and growth factors. In conclusion, although the issue of genetics pervades the entire discussion of host susceptibility, genes are not the only determinants of health and disease. Environmental factors may be equally important in shaping host susceptibility. Therefore, research must be focused on both the genetic bases and the environmental determinants of interstitial lung disease, in order to provide mechanism-based prevention strategies, early detection of, and improved therapy for these conditions.
Assuntos
Doenças Pulmonares Intersticiais/etiologia , Poluentes Atmosféricos/efeitos adversos , Suscetibilidade a Doenças , Exposição Ambiental/efeitos adversos , Humanos , Fatores de RiscoRESUMO
Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and in patients with obstructive chronic bronchitis (COPD-HI, n = 10) by analyses of the sol phase of spontaneously expectorated sputum (SSP). As compared with the CB-HI group, the COPD-HI group had significantly higher (p < 0.05) levels of myeloperoxidase (MPO) and tumor necrosis factor (TNF)-alpha in their SSP, whereas the degree of plasma protein leakage (SSP-to-serum ratio of plasma proteins) and the levels of interleukin (IL)-8, secretory IgA, and lactoferrin were similar in the two groups. These findings point to differences in pathophysiology in CB-HI and COPD-HI. The high level of TNF-alpha in the SSP of COPD-HI patients is in accord with the proposed role of TNF-alpha in the development of airway obstruction in COPD patients. In apparent contradiction, low levels of TNF-alpha were found in the SSP of noninfected but otherwise similar COPD patients (n = 9). This finding, however, does not exclude an exaggerated TNF-alpha response to infection or another stimulus in the airways of COPD patients. The SSP levels of MPO and IL-8, and the degree of plasma protein leakage in the COPD-HI group, were retrospectively compared with and found significantly higher than those of noninfected COPD patients, suggesting a more marked inflammatory response in COPD-HI. Whether this reflects a direct cause-and-effect relationship should be addressed in a future long-term prospective study involving repeated measurements in the same patients.