RESUMO
p-Chloromercuriphenylsulfonic acid (PCMS), a sulfhydryl inhibitor, prevented the mycelial-to-yeast transition of the dimorphic fungal pathogen, Histoplasma capsulatum. The effect of PCMS was specific for the mycelial-to-yeast transformation; it had no effect on growth of either the yeast or mycelial forms or on the yeast-to-mycelial transition. The failure of PCMS-treated mycelia to transform to yeast was permanent and irreversible. PCMS-treated mycelia could not infect mice but could stimulate resistance to infection by a pathogenic strain of Histoplasma capsulatum. These results suggest a new general strategy for vaccine development in diseases caused by dimorphic pathogens.
Assuntos
Histoplasma/fisiologia , 4-Cloromercuriobenzenossulfonato/farmacologia , Animais , Citocromos/metabolismo , Metabolismo Energético/efeitos dos fármacos , Proteínas Fúngicas/biossíntese , Histoplasma/efeitos dos fármacos , Histoplasma/patogenicidade , Histoplasmose/etiologia , Cinética , Camundongos , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacosRESUMO
We compared the mycelial to yeast transitions of the Downs strain of Histoplasma capsulatum (low level of virulence) with those of G184A and G222B, two more virulent strains having different levels of pathogenicity for mice. When the morphological transitions are initiated by a temperature shift from 25 degrees to 37 degrees C, all three strains undergo similar physiological changes, but these are less severe in G184A and G222B than in the Downs strain. The transitions from mycelial to yeast morphology in both of the more virulent strains are also one-third more rapid than in Downs. We also find that the differences in temperature sensitivity of the three strains can be correlated with the temperature required for complete uncoupling of oxidative phosphorylation. The differences in sensitivity to elevated temperatures extend to the growth of yeast cells of all three strains. Considered together, our results suggest that sensitivity to elevated temperatures may be a key factor accounting for differences in virulence and that uncoupling of oxidative phosphorylation may be the primary event in the morphological transition in all three strains.
Assuntos
Histoplasma/fisiologia , Temperatura , Trifosfato de Adenosina/análise , Animais , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Transporte de Elétrons , Histoplasma/patogenicidade , Camundongos , Camundongos Endogâmicos AKR , Consumo de Oxigênio , VirulênciaRESUMO
Considerable information has accumulated recently about specific genes of Histoplasma capsulatum that are expressed during the process of adaptation when the organism undergoes morphological transition at the onset of infection. The study of these genes is crucial to identify targets for the development of novel antifungal agents.
Assuntos
Histoplasma/fisiologia , Histoplasmose/microbiologia , Histoplasma/citologia , Histoplasma/genética , HumanosRESUMO
Kinetic experiments are reported showing that mammalian tyrosinase from B16 mouse melanoma is significantly activated by catalytic amounts of ferrous ions. Monitoring of tyrosine oxidation by both dopachrome formation and oxygen consumption showed that ferrous ions at micromolar concentrations induce a marked enzymatic activity with 0.01 U/ml of highly purified tyrosinase, whereas no detectable reaction occurs in the absence of metal over a sufficiently prolonged period of time. The extent of the activating effect, which is specific for the reduced form of iron, is proportional to the concentration of the added metal with a typical saturation profile, no further effect being observed beyond a threshold value. Changing the buffer system from phosphate to hepes or tris results in a marked decrease of the Fe2(+)-induced activation. Scavengers of active oxygen species, such as superoxide dismutase, catalase, formate and mannitol have no detectable effect on the tyrosinase activity. These results are accounted for in terms of an activation mechanism involving reduction of the cupric ions at the active site of the resting enzyme.
Assuntos
Catecol Oxidase/metabolismo , Compostos Ferrosos/farmacologia , Monofenol Mono-Oxigenase/metabolismo , Animais , Soluções Tampão , Ativação Enzimática/efeitos dos fármacos , Melanoma Experimental/enzimologia , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Consumo de Oxigênio/efeitos dos fármacos , Espectrofotometria , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/enzimologia , Células Tumorais Cultivadas/metabolismo , Tirosina/metabolismoRESUMO
Hypersecretion of mucus is the main feature of chronic bronchitis and is associated with an increased susceptibility to bronchial infections. Although airway inflammation is present in patients with chronic bronchitis and is recognised as a contributing factor in the development of bronchial hyper-reactivity and obstruction, the role of anti-inflammatory drugs in the treatment of chronic bronchitis has not been established. Nimesulide is a nonsteroidal anti-inflammatory drug that can modulate the function of neutrophils and block the effects of several inflammatory mediators. We found that a 3-week treatment course of nimesulide in patients with chronic mucus hypersecretion decreased sputum viscosity, thus significantly improving symptoms. The effect of nimesulide on the rheological properties of mucus was slower and weaker than that of classic mucolytics and was more likely to be related to a reduction in bronchovascular permeability. The clinical usefulness of nimesulide in chronic bronchitis deserves further investigation.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Bronquite/tratamento farmacológico , Sulfonamidas/uso terapêutico , Doença Crônica , HumanosRESUMO
Single photon emission computed tomography (SPECT) was performed with 99Tcm-albumin macroaggregates to study human pulmonary perfusion in healthy subjects and patients with respiratory diseases such as chronic obstructive pulmonary disease (COPD) and lung neoplasms. The reconstructed SPECT data was displayed in coronal, transverse, sagittal plane sections and compared to conventional perfusion scans. The SPECT data gave more complicated anatomical information about the extent of damage and morphology of the pulmonary vascular bed. In healthy subjects and COPD patients, qualitative and quantitative assessment of pulmonary perfusion could be obtained from serial SPECT scans with respect to distribution and relative concentration of the injected radiopharmaceutical. Furthermore, SPECT of pulmonary perfusion has been useful in detecting the extent of damage to the pulmonary circulation. This is useful for the preoperative evaluation and staging of lung cancer.
Assuntos
Pneumopatias Obstrutivas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Perfusão , Tomografia Computadorizada de Emissão , Adulto , Idoso , Carcinoma Broncogênico/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Agregado de Albumina Marcado com Tecnécio Tc 99mRESUMO
An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Azitromicina/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Bronquite/tratamento farmacológico , Quimioterapia Combinada/uso terapêutico , Idoso , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio , Azitromicina/efeitos adversos , Infecções Bacterianas/microbiologia , Bronquite/microbiologia , Doença Crônica , Ácidos Clavulânicos/efeitos adversos , Ácidos Clavulânicos/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escarro/microbiologiaRESUMO
The relationship between growth hormone deficiency (GHd) and ventilatory function is not well understood. We studied 7 patients with GHd since childhood who had been adequately treated with replacement therapy until cartilage fusion. Together with 7 well-matched (age and body-type) healthy control subjects, they underwent spirometry including determination of residual volume, and lung diffusing capacity. Also recorded were maximal respiratory muscle pressure during inspiration (PImax) and expiration (PEmax). Patients with GHd showed a significant reduction in total lung capacity and vital capacity while residual volume and lung diffusing capacity remained unchanged. All patients had a significant reduction of both PImax and PEmax. Previously treated adult subjects with GHd present a persistent decrease in lung mobilizing volumes associated with reduced respiratory muscle strength. These alterations may have implications in the management of GHd in adult patients.
Assuntos
Hormônio do Crescimento/deficiência , Respiração , Músculos Respiratórios/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Contração Muscular , Respiração/fisiologia , Testes de Função RespiratóriaRESUMO
Controlled short-term studies (< 6 months) have yielded conflicting results as to the steroid-sparing effect of methotrexate (MTX) and its effectiveness in treating patients with chronic corticosteroid-dependent asthma (CDA). In an open study, we treated 13 patients with MXT (7.5-20 mg.week-1) for > or = 12 months (range 54-72 weeks). After 12 weeks of treatment, the intake of steroids had fallen by 36 +/- 22% (mean +/- SD); the clinical score was not significantly different from baseline (1.7 +/- 0.44 vs 1.4 +/- 0.52). At 52 weeks, steroid intake was reduced by 87 +/- 23% and 9 of the 13 patients no longer required corticosteroids. Moreover, both the clinical and functional scores were significantly better with respect to run-in values forced expiratory volume in one second (FEV1) 75 +/- 6 vs 60 +/- 10% predicted; forced vital capacity (FVC) 84 +/- 10 vs 77 +/- 13% pred; arterial oxygen tension (PaO2) 11.3 +/- 1.0 vs 10.7 +/- 1.3 kPa (84.5 +/- 7.8 vs 80.6 +/- 9.6 mmHg). No serious side-effects were recorded during the study; transaminase levels were increased in 62% of cases. In patients affected by chronic corticosteroid dependent asthma, the steroid-sparing effects of methotrexate and clinical improvement were apparent after 6 months treatment.
Assuntos
Asma/tratamento farmacológico , Metotrexato/uso terapêutico , Prednisolona/uso terapêutico , Adulto , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Oxigênio/sangue , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Capacidade de Difusão Pulmonar/efeitos dos fármacos , Espirometria , Transaminases/sangue , Capacidade Vital/efeitos dos fármacosRESUMO
This paper deales with the applications of radionuclides to the study of human pulmonary circulation for better knowledge of some morphological and dinamic functional aspects. At this time the methods used are divided in three groups in respect to the purpose. - Methods for static investigations of pulmonary perfusion, by scintigraphy with radioalbum aggregates. - Methods for dynamic investigation, general radiocardiography and selective right radiocardiography with radioalbum macroaggregates. - Methods for morpho-functional investigation, especially Isotopoangiocardiopneumography using gamma-camera and Tc99mO4. Here are treated the fields of applications, the purpose and the limits of these methods, used in a large number of and acquired pulmonary vascular diseases.
Assuntos
Pulmão/diagnóstico por imagem , Circulação Pulmonar , Testes de Função Cardíaca/métodos , Humanos , Índio , Radioisótopos do Iodo , Pneumopatias/diagnóstico por imagem , Métodos , Técnica de Diluição de Radioisótopos , Radioisótopos , Cintilografia , Soroalbumina Radioiodada , TecnécioRESUMO
Tuelwe patients with asthma were studied by scintigraphic, and isotopoangiocardiographic technics under acute attack. No regionals differences in the pulmonary blood-flow distribution were observed. The results are help ful in the knowledge of ventilation/perfusion relationships and alterations of blood gases produced from asthma attack.
Assuntos
Asma/fisiopatologia , Circulação Pulmonar , Asma/diagnóstico por imagem , Coração/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Cintilografia , Soroalbumina Radioiodada , TecnécioRESUMO
The heat shock response is a general homeostatic mechanism that protects cells and the entire organism from the deleterious effects of environmental stress. It has been shown that heat shock proteins play major roles in many cellular processes and have a unique role in several areas of cell biology, from chronic degenerative diseases to immunology and from cancer research to interactions between host and parasite. In this review, Bruno Maresca and Luisella Carratu deal with some of the unique characteristics of the heat shock response in parasitic organisms.
RESUMO
Thallium-201 was given to 71 patients with various pulmonary diseases. Positive uptake was noted in primary malignant neoplasms and also in 6 cases of Hodgkin's lymphoma. No uptake was seen in pulmonary diseases other than active tuberculosis. A disadvantage is the high myocardial accumulation of this radionuclide which impairs proper visualization of paracardiac neoplasms.
Assuntos
Neoplasias Pulmonares/diagnóstico , Cintilografia , Tálio , Humanos , Radioisótopos , Tálio/metabolismoRESUMO
BACKGROUND: Nitric oxide has been detected by chemiluminescence in the lumen of nasal airway, which is increased in nasal breathing in patients with seasonal rhinitis during a chronic exposure. The purpose of this study was to determinate the effect of a NO-synthase inhibitor NGL-arginine methyl ester (L-NAME) on nasal airway resistance (NAR) in patients with seasonal allergic rhinitis after an acute challenge to the allergen. METHODS: Nitric oxide levels in the nose were measured by the chemiluminescence method in nine non-atopic volunteers and in seven patients with seasonal rhinitis at rest and after an acute challenge with the allergen. NAR were measured by active anterior rhinomanometry. RESULTS: Basal nasal NO concentration in allergic rhinitis was 496.5 +/- 151.4 parts per billion (ppb). (n = 7) and it was not significantly different from levels found in the control group: 458.4 +/- 105.9 ppb (n = 9). The topical administration of L-NAME in allergic rhinitis reduced the NO concentration (338.6 +/- 99.3 ppb, P < 0.001; n = 7). In the rhinitic patients the challenge with the allergen did not modify the nasal NO levels (504.5 +/- 138.5 ppb). The application of the allergen after the pretreatment with placebo caused a significant increase in NAR (from 0.32 +/- 0.11 Pa s cm-3 to 1.01 +/- 0.12 Pa s cm-3, P < 0.001; n = 7). Pre-treatment with L-NAME did not prevent the increase in NAR induced by allergen challenge (from 0.36 +/- 0.15 Pa s cm-3 to 1.06 +/- 0.26 Pa s cm-3). CONCLUSIONS: The results indicate that nasal administration of a NOS inhibitor L-NAME, at doses capable of decreasing nasal NO levels, has no effect on NAR and it does not prevent the NAR increase induced by an acute challenge with allergen in subjects with seasonal rhinitis.
Assuntos
Resistência das Vias Respiratórias , Alérgenos/administração & dosagem , Obstrução Nasal/metabolismo , Obstrução Nasal/fisiopatologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Rinite Alérgica Perene/metabolismo , Rinite Alérgica Perene/fisiopatologia , Administração Intranasal , Adulto , Resistência das Vias Respiratórias/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Obstrução Nasal/imunologia , Óxido Nítrico/metabolismo , Rinite Alérgica Perene/imunologiaRESUMO
BACKGROUND: The nose is an important source of nitric oxide (NO) in man, but the relevance of NO production to the response to inflammatory mediators is not clear. METHODS: In this study, we evaluated the effect of NO inhibition on nasal airway resistance (NAR) at baseline, after an acute challenge with platelet-activating factor (PAF), a potent proinflammatory factor, and after an acute challenge with bradykinin (BK), both of which are mediators of allergic rhinitis in man. Eight healthy subjects were enrolled in the study. Nasal NO production was measured by the chemiluminescence method, and NAR was measured by active anterior rhinomanometry. RESULTS: Basal nasal NO concentration was 500.6+/-115.6 ppb; it significantly decreased after topical administration of the NO-synthase inhibitor L-NAME, and the NO-synthase substrate L-arginine caused a recovery in NO production. The administration of L-NAME did not cause any change in basal NAR. In a double-blind fashion, we performed nasal challenge with PAF and BK after topical pretreatment with either placebo or L-NAME. After placebo pretreatment, both PAF and BK caused a significant increase in NAR (respectively, from 0.29+/-0.11 Pa s cm(-3) to 0.75+/-0.21 Pa s cm(-3), and from 0.36+/-0.18 Pa s cm(-3) to 0.71+/-0.25 Pa s cm(-3); P<0.001, n=8). Pretreatment with L-NAME did not prevent the PAF-induced increase in NAR (from 0.31+/-0.10 Pa s cm(-3) to 0.71+/-0.27 Pa s cm(-3)), whereas it prevented the BK-induced increase in NAR (from 0.33+/-0.15 Pa s cm(-3) to 0.43+/-0.16 Pa s cm(-3)). CONCLUSIONS: Topical administration of the NO-synthase inhibitor L-NAME at doses sufficient to decrease NO nasal production does not prevent the PAF-induced increase in NAR, indicating that NO generation in vivo is not involved in the nasal response to PAF.
Assuntos
NG-Nitroarginina Metil Éster/farmacologia , Obstrução Nasal/induzido quimicamente , Óxido Nítrico/fisiologia , Fator de Ativação de Plaquetas/farmacologia , Adulto , Resistência das Vias Respiratórias/efeitos dos fármacos , Bradicinina/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Obstrução Nasal/metabolismo , Testes de Provocação Nasal , Óxido Nítrico Sintase/antagonistas & inibidoresRESUMO
BACKGROUND: Paranasal sinuses and the nose are important sources of nitric oxide (NO) in humans but the relevance of NO production to the control of nasal airway plasma exudation and its response to inflammatory mediators such as platelet-activating factor (PAF) in healthy subjects is not well known. DESIGN: In this study we aimed to evaluate the effect of the nitric oxide synthase (NOS) inhibitor NG L-arginine methyl ester (L-NAME) on nasal airway plasma extravasation at baseline and after an acute challenge with PAF that induces most symptoms of rhinitis. Eleven healthy subjects were enrolled in the study. Plasma extravasation in the nasal airway was assessed by measuring the albumin content of nasal lavage. RESULTS: PAF challenge caused a significant increase in concentrations of albumin in the nasal lavage fluid (from 0.59 +/- 0.13 mg dL(-1) to 2.46 +/- 0.45 mg dL(-1)) after placebo. Pretreatment with L-NAME significantly prevented the increase of albumin in the nasal lavage fluid induced by PAF as compared to placebo (from 0.53 +/- 0.11 mg dL(-1) to 1.70 +/- 0.28 mg dL(-1); P < 0.005). CONCLUSION: Topical administration of a NO inhibitor is able to attenuate the nasal airway plasma extravasation induced by PAF, suggesting that NO release in vivo is involved in the nasal response to PAF.
Assuntos
NG-Nitroarginina Metil Éster/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Pré-Medicação , Rinite/prevenção & controle , Administração Intranasal , Adulto , Albuminas/análise , Método Duplo-Cego , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Masculino , Líquido da Lavagem Nasal/química , Fator de Ativação de Plaquetas , Rinite/metabolismo , Estatísticas não ParamétricasRESUMO
In this brief review the results of the most important studies about smoking and cardiovascular diseases are referred. Epidemiological, pathological, and clinical data show an higher mortality from coronary heart diseases in smokers, and an higher frequency of atherosclerothic lesions, affecting all types of sistemic vessels. By an analysis of the tobacco smoke composition, some of the effects and acting mechanism of nicotine and Carbone Monoxideon the cardiocirculatory system are treated. It is remarkable that cigarette smoke is only a "risk factor" and overall together other conditions as hypertension or dyslipidamia.
Assuntos
Doenças Cardiovasculares/etiologia , Idoso , Arteriosclerose/etiologia , Arteriosclerose/patologia , Monóxido de Carbono/toxicidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Sistema Cardiovascular/efeitos dos fármacos , Doença das Coronárias/etiologia , Doença das Coronárias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/análise , Nicotina/toxicidade , Plantas Tóxicas , Fumaça/análise , Fumar , Nicotiana/análiseRESUMO
Endothelin (ET) is an endothelial regulatory peptide present also in pulmonary tissue where it exerts several biological actions both on bronchial and vascular smooth muscle cells. It has been shown to increase in bronchoalveolar lavage fluid (BALF) from asthmatic patients; but changes in other chronic respiratory disease have not been well studied. We measured by a radioimmunoassay (RIA) ET-immunoreactive (IR) levels on BALF (BALF-ETIR, pg/ml) from 5 normal subjects (NS), 5 patients with chronic extrapulmonary disease (ED) without signs of lung involvement, 5 patients with allergic bronchial asthma (BA), 10 patients with idiopathic lung fibrosis (ILF) and 9 patients with miscellaneous interstitial lung disease (MILD). In 5/5 NS and 4/5 ED BALF-ETIR was lower than sensibility of RIA test used (0.8 pg/ml). BALF-ETIR was dosable in all patients with bronchopulmonary disease; means were 2.45 pg/ml in BA, 12.37 pg/ml in ILF, 2.90 pg/ml in MILD--Wilcoxon's rank test (two tailed) versus NS, p < 0.05. There was an inverse correlation between BALF-ETIR values and the degree of ventilatory impairment (forced vital capacity % of predicted value, r = -0.61 p < 0.01; forced expiratory volume in 1 s % of predicted value, r = -0.71 p < 0.01) and the level of arterial pressure of O2 (PaO2; r = -0.75 p < 0.01); a positive correlation was found with number of neutrophils/ml of BALF (r = 0.52 p < 0.01)--Spearman's rank correlation. Though rarely detected on BALF from normal lungs, ET increases on BALF in patients with bronchopulmonary disease, raising the question of its involvement in pathogenic mechanisms or evolution of bronchial asthma and interstitial lung disease.
Assuntos
Asma/metabolismo , Líquido da Lavagem Broncoalveolar/química , Endotelinas/análise , Fibrose Pulmonar/metabolismo , Adulto , Asma/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/diagnóstico , Radioimunoensaio , Testes de Função RespiratóriaRESUMO
BACKGROUND: It has been recently shown that humming greatly increases nasal nitric oxide (NO). This is most likely owing to a rapid washout of sinus NO caused by the oscillating sound waves. During repeated humming manoeuvres nasal NO gradually decreases, likely because NO accumulated in the sinuses is washed out. AIM: We studied whether humming before measurements would affect nasally exhaled NO. MATERIALS AND METHODS: NO output was measured by the chemiluminescence technique in orally and nasally exhaled air in 38 subjects: 18 healthy subjects (HS), 15 subjects with allergic rhinitis (AR) and five subjects with allergic nasal polyposis (AP). Each subject performed a NO measurement during quiet nasal exhalation either preceded by a period of silence/free speaking or immediately after five consecutive humming manoeuvres (posthumming). RESULTS: Mean nasal NO output (95% CI) after a period of silence/free speaking was 231 nL min-1 (178-284) in HS, 434 nL min-1 (347-522) in AR (P < 0.001) and 262 nL min-1 (163-361) in AP. Post-humming nasal NO output was 16% (5 to 50%) lower in HS and 14% (1 to 49%) lower in AR, while it remained unchanged in AP subjects. Intra-subject coefficient of variation of quiet nasal exhalation was 12% in HS, 13% in AR and 5% in AP. Post humming intraindividual coefficient of variation significantly decreased in both HS and AR, but it did not change in AP. CONCLUSIONS: Nasal NO levels measured immediately after repeated humming manoeuvres are consistently lower and more reproducible than nasal NO levels measured after a period of silence or free speaking. Repeated humming effectively empties the sinuses, thereby probably minimizing the normal contribution from the sinuses to nasal NO. This may be useful to better estimate NO output from the nasal cavity mucosa in health and disease.