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Biomedical subjects

A Spanevello

Publications and source records attributed to A Spanevello.

At least 19 recordsLinked to original sources

Induced sputum in children: feasibility, repeatability, and relation of findings to asthma severity.

BACKGROUND: The collection of induced sputum provides a non-invasive method of investigating airway inflammation. Few studies have been performed in children, so a study was undertaken to determine the feasibility of sputum induction, the repeatability of eosinophil counts and sputum eosinophil cationic protein (ECP) levels, and the relation of these to current asthma severity. For comparison, serum ECP levels were also measured. METHODS: In a cross sectional study of children aged 5-15 years, 27 healthy children and 60 with asthma underwent sputum induction using inhaled nebulised hypertonic saline. The whole sputum sample was used for analysis. Ten children with stable asthma repeated the procedure within 10 days. RESULTS: A satisfactory sample (>500 non-squamous cells) was obtained in 61% of children with asthma and in 60% of healthy controls. The limits of agreement within subjects ranged from a 0.68 to 2.8 fold difference for eosinophil differential counts and from 0.38 to 4.4 fold for sputum ECP. Despite a median of 42% squamous cells, significant differences were found between asthma and healthy controls for the eosinophil differential count (p = 0.0004), total eosinophil counts (p = 0.03), and sputum ECP level (p = 0.0001). Overall, there was no correlation between any marker of airway inflammation and asthma severity, however expressed, including lung function. CONCLUSIONS: Sputum induction is only possible in a proportion of children. The repeatability of sputum cell counts and ECP levels, measured in a small number of children, was similar to that reported in adults. Sputum analysis revealed no evidence of airway inflammation in a number of highly symptomatic children with asthma.

Adolescent↗

Induced sputum cellularity. Reference values and distribution in normal volunteers.

Sputum induction has recently been proposed as the only direct noninvasive method for measuring airway inflammatory indices. The reference values and the distribution of cells in induced sputum in a control population have not yet been well defined. We therefore evaluated data from a large number of healthy volunteers. One hundred fourteen healthy, nonatopic, nonsmoking volunteers without airway hyperreactivity were enrolled (age: 38 +/- 13 yr [mean +/- SD]; FEV(1): 105 +/- 10% predicted; provocative dose of methacholine inducing a 20% decrease FEV(1) > 3,200 microgram). Ninety-six subjects (84%) produced adequate analysis samples. The subjects had a normal age distribution. Their induced sputum was rich in macrophages (69.2 +/- 13%) and neutrophils (27.3 +/- 13%), and poor in eosinophils (0.6 +/- 0.8%), lymphocytes (1.0 +/- 1.2%), and epithelial cells (1.5 +/- 1.8%). Only macrophages and neutrophils showed a normal distribution; total and differential counts of other cells did not. We propose that these data be used in comparison of the induced sputum cells of normal subjects and those of patients with airway inflammation.

Adult↗

Effect of methacholine challenge on cellular composition of sputum induction.

BACKGROUND: Induced sputum and methacholine inhalation challenge are routinely used for the assessment of airway inflammation and airway hyperresponsiveness, respectively. This study investigates whether a methacholine challenge performed one hour before sputum induction alters the cellular and biochemical constituents of sputum. METHODS: Sixteen stable asthmatic patients with lung function within the normal range underwent two sputum inductions within one week. One hour before one of the sputum inductions a methacholine challenge was performed. RESULTS: There were no significant differences in total cell count, macrophages, neutrophils, eosinophils, lymphocytes, epithelial cells, ECP, and albumin between the two challenges. The repeatability of cell counts was good for all cells, ECP and albumin, but poor for total cells. CONCLUSIONS: In patients with stable asthma a methacholine challenge carried out one hour before sputum induction does not significantly alter the cellular and biochemical constituents of sputum.

Adolescent↗

Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation.

We determined the dose-response curves to inhaled methacholine (MCh) in 16 asthmatic and 8 healthy subjects with prohibition of deep inhalations (DIs) and with 5 DIs taken after each MCh dose. Flow was measured on partial expiratory flow-volume curves at an absolute lung volume (plethysmographically determined) equal to 25% of control forced vital capacity (FVC). Airway inflammation was assessed in asthmatic subjects by analysis of induced sputum. Even when DIs were prohibited, the dose of MCh causing a 50% decrease in forced partial flow at 25% of control FVC (PD(50)MCh) was lower in asthmatic than in healthy subjects (P < 0.0001). In healthy but not in asthmatic subjects, repeated DIs significantly decreased the maximum response to MCh [from 90 +/- 4 to 62 +/- 8 (SD) % of control, P < 0.001], increased PD(50)MCh (P < 0.005), without affecting the dose causing 50% of maximal response. In asthmatic subjects, neither PD(50)MCh when DIs were prohibited nor changes in PD(50)MCh induced by DIs were significantly correlated with inflammatory cell numbers or percentages in sputum. We conclude that 1) even when DIs are prohibited, the responsiveness to MCh is greater in asthmatic than in healthy subjects; 2) repeated DIs reduce airway responsiveness in healthy but not in asthmatic subjects; and 3) neither airway hyperresponsiveness nor the inability of DIs to relax constricted airways in asthmatic subjects is related to the presence of inflammatory cells in the airways.

Administration, Inhalation↗

Savings obtained using an oxygen economizer device: a cost-minimization analysis.

As liquid oxygen represents a relevant burden on healthcare systems, different methods have been developed to reduce oxygen consumption, including economizers. The aims of the study were: 1) to evaluate the efficacy of an economizer device (Companion 5 Oxygen Saver) in a significant sample of patients, and 2) to perform cost-minimization analysis of the possible savings to be obtained using the device. The study was designed as an open, prospective clinical trial in which equivalence in haemoglobin saturation with and without the economizer device was demonstrated, preliminary to cost-minimization analysis in patients affected by restrictive and obstructive lung disease. Patients were to use their usual O2 flow, provided it was able to guarantee a saturation of > or = 90% and an arterial oxygen tension (Pa,O2) of > or = 8.0 kPa (60 mmHg) during rest, sleep and exercise with and without the economizer (mean value and different saturation ranges compared by means of parametric or nonparametric tests where appropriate). The average unit cost was calculated with and without the economizer, based on the average unit O2 consumption, and cost-minimization analysis was performed. In 29 patients enrolled, the mean (+/- SD) O2 flow in L.min-1 was 1.5 +/- 0.6 during sleep, 1.4 +/- 0.6 during rest and 2.3 +/- 1.1 during exercise. The mean oxygen saturation during sleep was 91.2 +/- 19.5% without and 97.2 +/- 3.9% with the economizer device (p = 0.09), the mean saturation during rest was 88.8 +/- 22.7% without and 92.1 +/- 14.9% with the economizer device (p = 0.42), and the mean saturation during exercise was 84.7 +/- 19.3% without and 91.8 +/- 15.9% with the economizer device (p = 0.04). The total daily O2 consumption was significantly lower using the economizer device (2,384 +/- 950.3 versus 93.0 +/- 482.9 L, p < 0.001). The potential savings, estimated per patient per year, were 530,114 +/- 184,233 L, corresponding to US$2,492 +/- 866. During the first year the total unit savings would be US$1,892. The savings, consistently relevant alongside the whole range of variation explored by sensitivity analysis both during the first and the following years, justify considering the adoption of similar economizers on a larger scale, although further studies should be performed to evaluate whether or not liquid oxygen really represents the most cost-effective method of treating hypoxaemic patients.

Aged↗

Bronchoalveolar lavage causes decrease in PaO2, increase in (A-a) gradient value and bronchoconstriction in asthmatics.

The aims of this study were to (1) record the changes of (arterial oxygen partial pressure) PaO2, (arterial carbon dioxide partial pressure) PaCO2, (percentage saturation of haemoglobin with oxygen in arterial blood) SaO2 and alveolar-arterial (A-a) oxygen gradiant resulting from bronchoalveolar lavage (BAL) in asthmatic and normal subjects; (2) measure changes in forced expiratory volume in 1 s (FEV1), vital capacity forced (FVC) associated with BAL; and (3) assess possible predictive factors for the degree of hypoxaemia and impairment of spirometry resulting from BAL. Bronchoscopy and BAL (150 ml) were performed in 24 asthmatics and 15 healthy subjects. Serial arterial blood samples (radial artery) were obtained in all subjects: T1 and before T2 after local anaesthesia; T3 at end of bronchoscopy; T4 after BAL and 5 min, 15 min, 1 h, 2 h, 8 h and 24 h (T5-T10) after the procedure, FEV1 and FVC were measured immediately before and 5 min afer bronchoscopy. Baseline PaO2 was lower in asthmatics (10.2 +/- 0.8 kPa) than in healthy subjects (10.8 +/- 0.8). Both groups showed a significant decrease in PaO2, and a significant widening in (A-a) oxygen tension gradiant at T3-9, with respect to T1 (P < 0.05). PaO2 reached a significantly lower value in asthmatics (7.1 +/- 0.6 kPa) than in HS (7.7 +/- 0.5; P < 0.05). In asthmatics, FEV1, FVC and the ratio FEV1/FVC decreased significantly after BAL (P < 0.001). In healthy subjects, FEV1 and FVC decreased significantly (P < 0.001), whereas FEV1/FVC did not. The fall in FEV1 after BAL was significantly greater in asthmatics (32.4 +/- 10.0%) than in healthy subjects (17.7 +/- 4.6; P < 0.001). Severity of asthma, basline FEV1 or initial PaO2 did not predict the degree of hypoxaemia or the fall of FEV1. It is concluded that BAL causes more severe hypoxaemia and a greater decrease in FEV1 in asthmatics compared to healthy subjects, strongly supporting the recommendation of special caution and careful monitoring when BAL is undertaken in asthmatics.

Analysis of Variance↗

Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease.

BACKGROUND: Airways inflammation is a feature of chronic obstructive pulmonary disease (COPD), but the role of corticosteroids in the management of clinically stable patients has yet to be established. A randomised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate (BDP) administered for two months to patients with stable, smoking related COPD. Sputum induction was used to evaluate bronchial inflammation response. METHODS: 34 patients (20 men and 14 women) were examined on three separate occasions. At the initial clinical assessment (visit 0), spirometry and blood gas analysis were performed. On visit 1 (within one week of visit 0) sputum induction was performed and each patient was randomised to receive either BDP 500 micrograms three times daily (treated group) or nothing (control group). After two months (visit 2), all patients underwent repeat clinical assessment, spirometry, and sputum induction. RESULTS: There were no differences in sputum cell counts between the groups at baseline. After two months of treatment, induced sputum samples from patients in the treated group showed a reduction in both neutrophils (-27%) and total cells (-42%) with respect to baseline, while the control group did not (neutrophils +9%, total cells +7%). Macrophages increased in the treated group but not in the control group. The mean final value of sputum neutrophils was 52% in the treated group and 73.3% in the control group (95% confidence interval (CI) -27.2 to -15.4). The mean final value of sputum macrophages was 35.8% in treated group and 19.3% in control group (95% CI 10.3 to 22.8). The differences between the treated and control groups for neutrophils (-21.3%), macrophages (+16.5%), and total cells (-65%) were significant. Spirometry and blood gas data did not change from baseline in either patient group. CONCLUSIONS: A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation.

Administration, Inhalation↗

Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma.

In asthma, the acute increment of airway responsiveness caused by exposure to allergen is associated with influx of eosinophils into the airways. The relationship between chronic airway hyperresponsiveness and airway inflammation is unclear, as they do not change consistently following long-term anti-inflammatory treatments. We studied 71 patients with chronic asthma and allergic sensitization to perennial allergens. Airway responsiveness was determined by inhalation of methacholine, and airway inflammation was quantified by induced sputum (n = 28) or bronchoalveolar lavage (n = 43) and bronchial biopsy (n = 20). The relationships between airway responsiveness and the numbers of different inflammatory cells were assessed by multiple regression analysis. No significant correlations were found between the degree of airway responsiveness and the numbers of inflammatory cells in sputum or bronchoalveolar lavage or bronchial biopsy. By contrast, baseline lung function was inversely related to the numbers of eosinophils and directly related to the numbers of macrophages. The eosinophil cationic protein contents of either sputum or bronchoalveolar lavage were significantly correlated with the percentages of eosinophils but not with airway responsiveness. We suggest that other factors (e.g., airway wall remodeling or autonomic dysfunction) may be responsible for most of the interindividual variability of airway responsiveness in asthma.

Adult↗

Comparison of two methods of processing induced sputum: selected versus entire sputum.

Sputum analysis is increasingly used to assess airway inflammation in asthma. The analysis of sputum is currently performed with two techniques, i.e., analysis of selected sputum (plugs) and analysis of entire sputum. To investigate the diagnostic value of these two methods, we compared total and differential cell counts and supernatant eosinophil cationic protein (ECP) in selected and entire sputum collected on two occasions in a group of healthy and asthmatic subjects. We induced sputum with hypertonic saline in 18 asthmatics and in eight healthy subjects. On one occasion we analyzed selected sputum, and on another occasion we analyzed entire sputum. In each sample we measured total and differential cell counts and ECP concentration in supernatant. We found a higher percentage of eosinophils (15.3 versus 8.3%; p < 0.01), more viable nonsquamous cells (80.6 versus 71.8%; p < 0.01), and higher levels of ECP (548 versus 105 microg/L; p < 0.001) in selected sputum as compared with entire sputum, whereas the percentage of neutrophils was higher in the entire sputum (42.7 versus 33.3%; p < 0.05). The percentage of eosinophils and ECP concentration were significantly and similarly increased in both selected and entire sputum of asthmatic subjects, i.e., independent of the method of sputum analysis. In conclusion, the selected sputum method may indeed provide more viable cells, more eosinophils, and a higher concentration of ECP. However, both the selected sputum and the entire sputum method have the same diagnostic value in distinguishing asthmatics from healthy subjects.

Adult↗

Surveillance of tuberculosis treatment prescription in Italy. The Varese TB Study Group.

In industrialized countries, data on antituberculosis treatment are scanty. The aim of this study was to describe the tuberculosis (TB) treatment programme from diagnosis to drug intake in a model area of northern Italy, evaluating: 1) antiTB regimens prescribed and their adequacy; 2) dosage of drugs; 3) side-effects; and 4) drug resistance. Individual data on new TB cases from all the existing health facilities of the area were collected by means or a prospective surveillance system based on the systematic review of original clinical forms. Regimens were classified as adequate, potentially adequate and inadequate, based on published recommendations. Data on drug dosage, side effects and drug resistance were analysed. Out of 109 TB cases with regimen recorded on clinical records, 20.2% included more than four major drugs, 63.3% three drugs and 16.5% two drugs. The regimens were classified as 1.8% adequate, 85% potentially inadequate and 12.8% inadequate. The dosages prescribed (mean +/- SD in mg.kg body weight-1.day-1) were: isoniazid: 6.8 +/- 2.7: rifampicin: 10.2 +/- 2.5; ethambutol: 21.3 +/- 4.5; streptomycin: 17.4 +/- 4.0: and pyrazinamide: 15.2. Twelve per cent of cases required treatment modification due to side-effects. Resistance to one single drug was found in 9% of cases, but no case with multidrug-resistant TB. The description of the treatment programme revealed that: 1) the majority of regimens are potentially adequate; 2) they are at a proper dosage; 3) the side-effects are in agreement with the literature; and 4) drug-resistance rates are low.

Antitubercular Agents↗

Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance.

This study aimed to investigate the relationship between skeletal muscle, fibre type composition, functional respiratory impairment and exercise tolerance in patients with moderate to severe chronic obstructive pulmonary disease (COPD). A group of 22 COPD patients and 10 healthy control subjects were studied. In COPD patients, vital capacity (VC) and forced expiratory volume in one second (FEV1) were reduced to 79% and 51%, respectively. Diffusion indices (transfer factor of the lung for carbon monoxide (TL,CO) and carbon monoxide transfer coefficient (KCO)) were also reduced. Arterial oxygen tension (Pa,O2) was normal or slightly altered. A maximal exercise test was performed and anaerobic threshold was calculated. Muscle samples from vastus lateralis were obtained by needle biopsy. Myosin heavy chain (MHC) and light chain (MLC) isoforms were separated by gel electrophoresis and quantified by densitometry. MHC isoforms were considered as molecular markers of fibre types. The proportion of the fast MHC-2B isoform was increased in COPD patients. TL,CO, KCO, VC and FEV1 were positively correlated with slow MHC isoform content. TL,CO and KCO were also negatively correlated with the content of the fast MHC-2B isoform. No correlation was found between exercise parameters and MHC isoform composition. The co-ordinated expression between MHC and MLC isoforms was altered in COPD patients. We conclude that reduced oxygen availability, probably in combination with muscle disuse, may determine muscle alterations in chronic obstructive pulmonary disease patients. The altered correlations between myosin heavy chain and light chain isoforms suggest that co-ordinated protein expression is lost in chronic obstructive pulmonary disease muscles.

Adult↗

Induced sputum to assess airway inflammation: a study of reproducibility.

BACKGROUND: Infiltration of the airways mucosa with activated inflammatory cells appears to be a major factor in the pathogenesis of asthma and other airway diseases. Examination of sputum provides a direct method to investigate airway inflammation non-invasively. OBJECTIVES: The aim of the present study was to evaluate the reproducibility of cell counts on cytospins and fluid phase (eosinophil cationic protein, ECP) measurements in a selected portion of induced sputum. We aimed to confirm the validity of the tecnique by comparing measurements between stable asthmatics, allergic rhinithis and healthy subjects. METHODS: Sputum was induced with hypertonic saline (4.5%) twice within one week in 53 stable asthmatics, 16 subjects with seasonal rhinitis (out of the pollen season), and 19 healthy subjects. Reproducibility was examined within sample (two different plugs of the same sample) between sample (two specimens of induced sputum obtained within one week) and between examiners on stable subjects taking into account sample size, number of examinations per patients and Confidence Interval (CI) of the estimates. RESULTS: We have found that the method is highly reproducible within sample and between examiners for all types of cells and fluid phase measurements of ECP. It is reproducible between sample for eosinophils, macrophages, neutrophils and ECP, but not for lymphocytes and weakly for epithelial cells. Sputum from asthmatics, in comparison with the sputum of healthy subjects and subjects with rhinitis had higher eosinophils (asthmatics: 12.2% +/- 12.9, rhinitis: 0.4 +/- 0.8, normals: 0.4 +/- 0.7 (%) and ECP (asthmatics: 827 +/- 491 microg/L, rhinitis: 127 +/- 82 normals: 157 +/- 203). No significant differences were found between healthy subjects and subjects with rhinitis. Eosinophil counts were inversely correlated with FEV1 (r = -0.37) expressed as percentage of predicted, but not significantly correlated with PC20 methacholine (r = -0.28) or blood eosinophils (r = 0.26). CONCLUSIONS: The importance of this study is the confirmation, within important statistical guidelines for a study of reproducibility, that the methods examined are reproducible and valid.

Adult↗

AIDS and tuberculosis control programmes: an integrated approach at educational level.

In developing countries with a high prevalence of individuals co-infected by human immunodeficiency virus (HIV) and tuberculosis (TB), urgent public health measures should be implemented to prevent the spread of both diseases. This study was performed by a combined acquired immune deficiency syndrome (AIDS)-TB health team with the following aims: 1) to assess knowledge, attitudes and practice towards AIDS; 2) to identify target groups for health education (HE); 3) to evaluate HE impact; 4) to circulate correct information on AIDS and TB through target groups; and 5) to evaluate integration of AIDS and control TB activities. Secondary school students of Arua District, Uganda, participated in a standardized HE session (covering the key-points of AIDS and TB control) preceded by a pretest (multiple choice) questionnaire and followed 3 months later by the same questionnaire (post-test). The impact of HE on AIDS control was evaluated by comparing answers to pre- and post-test questionnaires and its influence on the TB programme by evaluating case-finding performances in the period preceding and following the survey. We analysed 1,478 questionnaires. The results of our study gave information on knowledge about AIDS, identified females and students < 16 yrs of age as good targets for HE, revealed that the impact of HE was significantly associated with improved knowledge, contributed to improved TB case-finding and offered suggestions for the integration of programmes. The survey represented an opportunity to create a stable AIDS/TB health team at district level.

Acquired Immunodeficiency Syndrome↗

Computerized patient record for a department of respiratory rehabilitation.

A computerized patient record (CPR) system plays an essential support role in the efficient functioning of the clinical and research services of a medical centre. We report the experience gained in developing a CPR for the Respiratory Rehabilitation Department (RRD) of the Tradate Medical Center of the Salvatore Maugeri Foundation, with specific reference to Out-patient (OP) and In-patient (IP) Units. The CPR was developed locally under the guidance of the Bioengineering Department. Several items implemented and strategies adopted are described and grouped in relation to broader objectives, such as the improvement of health-care quality, the enhancement of personnel productivity and reduction in costs, the support of clinical and health service research and the accommodation of future developments. In particular, we describe the design and implementation of anamnestic, physical and admission data collection, specifically orientated to respiratory diseases. Daily use of the CPR in the OP and IP units and its potential outcome for research and management support are also studied in detail. On the basis of our experience (1,251 out-patient examinations, 650 in-patient clinical admission cards), the computerized patient record seems a useful way of providing better health-care and a more comprehensive coverage of the rehabilitation process of patients in a Respiratory Rehabilitation Department.

Delivery of Health Care↗

Evaluation of the impact of guidelines on tuberculosis control in Italy. National AIPO "Tuberculosis" Study Group. Associazione Italiana Pneumologi Ospedalieri.

This study was performed in Italy, where a central tuberculosis (TB) unit and national guidelines on TB control are lacking. The objectives of the study were: 1) to design comprehensive guidelines on TB control; 2) to discuss them within the scientific community and to present them to administrators and politicians: and 3) to evaluate their impact from a public health perspective. The ultimate goal was to improve TB control nationwide through a consensus-based initiative. The steps taken in planning were as follows: 1) an assessment of control activities operating in the country was made by means of three surveys: 2) guidelines on TB control were designed, presented, discussed and approved during three Consensus Conferences involving representatives of organizations operating in TB control and services; and 3) their impact was evaluated by means of objectively verifiable indicators (availability of TB case definition, regional control programmes, surveillance reports, guidelines on treatment, staff training). Regional TB control programmes were implemented in three major regions (30% of the national population), and are in advanced process in other four regions (29% of the national population). The protocol approved during the three Consensus Conferences benefited from the co-ordinated action of governmental and nongovernmental organizations. Its impact on tuberculosis control was positive, particularly at the regional level.

Consensus Statements as Topic↗

Economic analysis of two structured treatment and teaching programs on asthma.

The aims of the present study were as follows: 1) to evaluate the medical outcomes of two treatment and educational asthma programs 2) to determine by cost-analysis both cost and economic outcome of the programs 3) to perform a cost-benefit analysis (determining the net cost-benefit) and a cost-effectiveness analysis (determining the cost per unit of effect and the incremental cost-effectiveness ratio) from the perspective of health program policy makers (HPP; indirect costs, i.e., loss of productivity, excluded) and of society as a whole (SaW, all costs included). Patients were randomly assigned to a complete (CP; n = 32) or reduced (RP; n = 33) program: the RP group received a reduced education (self-reading of an educational booklet on asthma), while the CP group attended an "asthma school", consisting of six lessons based on the same booklet and including educational videotapes. Both programs included peak-flow monitoring and treatment according to international guidelines, and follow-up. The outcome variables (asthma attacks, urgent medical examinations, admission days, working days lost) did not differ significantly between CP and RP. Morbidity savings were $1894.70 (CP) and $1697.80 (RP) according to SaW, and $1349.50 and $1301.80, respectively, according to HPP. The net cost-benefit was $1181.50 for CP and $1028.00 for RP, and the cost-benefit ratio per dollar spent was 1:2.6 for CP and 1:2.5 for RP, according to SaW. One day of admission prevented had a cost of $110.20 (CP) and $94.10 (RP). CP gave slightly better results and was slightly more cost-effective than RP in improving patients' welfare. It cannot be excluded that the retrospective analysis used to determine baseline costs might have inflated differences for both groups. Sensitivity analysis was slightly in favor of RP when the outcome variables were tested at their upper and lower 95% CI.

Adult↗

Effects of intradermal injection of atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) causes mast cell degranulation in rats in vivo and in vitro but is bronchodilator in humans. The aim of this study was to investigate the wheal and flare dose-response to intradermal injection of alpha-human ANP in normal humans. Eight normal subjects received five 30 microliters injections containing 1, 10, 39, 78, 117 pmol ANP and one each of normal saline, histamine 675 pmol and substance P 30 pmol. Maximum ANP flare response was greater but not significantly than that to saline at 1.55 +/- 0.6 (mean +/- s.e. mean) compared with 0.42 +/- 0.17 cm2, but much less than to histamine 9.86 +/- 0.97 or to substance P 12.5 +/- 1.2. Maximum ANP wheal response was significantly greater than that to saline at 0.38 +/- 0.08 compared with 0.18 +/- 0.05 cm2 (difference between means 0.20, 95% CI 0.05, 0.35), but much less than to histamine 0.75 +/- 0.06 or to substance P 1.05 +/- 0.08 cm2. No dose-response to ANP was demonstrated, though responses to the highest dose differed significantly from those to the lowest dose studied. We conclude that human cutaneous responses to ANP differ from those of animals and that the skin is less responsive than other tissues in humans.

Adult↗