Exhaled particles and small airways.

BACKGROUND: Originally, studies on exhaled droplets explored properties of airborne transmission of infectious diseases. More recently, the interest focuses on properties of exhaled droplets as biomarkers, enabled by the development of technical equipment and methods for chemical analysis. Because exhaled droplets contain nonvolatile substances, particles is the physical designation. This review aims to outline the development in the area of exhaled particles, particularly regarding biomarkers and the connection with small airways, i e airways with an internal diameter < 2 mm. MAIN BODY: Generation mechanisms, sites of origin, number concentrations of exhaled particles and the content of nonvolatile substances are studied. Exhaled particles range in diameter from 0.01 and 1000 µm depending on generation mechanism and site of origin. Airway reopening is one scientifically substantiated particle generation mechanism. During deep expirations, small airways close and the reopening process produces minute particles. When exhaled, these particles have a diameter of < 4 µm. A size discriminating sampling of particles < 4 µm and determination of the size distribution, allows exhaled particle mass to be estimated. The median mass is represented by particles in the size range of 0.7 to 1.0 µm. Half an hour of repeated deep expirations result in samples in the order of nanogram to microgram. The source of these samples is the respiratory tract ling fluid of small airways and consists of lipids and proteins, similarly to surfactant. Early clinical studies of e g chronic obstructive pulmonary disease and asthma, reported altered particle formation and particle composition. CONCLUSION: The physical properties and content of exhaled particles generated by the airway reopening mechanism offers an exciting noninvasive way to obtain samples from the respiratory tract lining fluid of small airways. The biomarker potential is only at the beginning to be explored.

Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study.

BACKGROUND: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). MATERIALS AND METHODS: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50-64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 µg of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to "Have you ever had asthma diagnosed by a physician?". Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker. RESULTS: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. CONCLUSION: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is ~9%, 4% and 5%, respectively.

Determination of ethane, pentane and isoprene in exhaled air--effects of breath-holding, flow rate and purified air.

AIM: Exhaled ethane, pentane and isoprene have been proposed as biomarkers of oxidative stress. The objectives were to explore whether ethane, pentane and isoprene are produced within the airways and to explore the effect of different sampling parameters on analyte concentrations. METHODS: The flow dependency of the analyte concentrations, the concentrations in dead-space and alveolar air after breath-holding and the influence of inhaling purified air on analyte concentrations were investigated. The analytical method involved thermal desorption from sorbent tubes and gas chromatography. The studied group comprised 13 subjects with clinically stable asthma and 14 healthy controls. RESULTS: Ethane concentrations decreased slightly, but significantly, at higher flow rates in subjects with asthma (P = 0.0063) but not in healthy controls. Pentane levels were increased at higher flow rates both in healthy and asthmatic subjects (P = 0.022 and 0.0063 respectively). Isoprene levels were increased at higher flow rates, but only significantly in healthy subjects (P = 0.0034). After breath-holding, no significant changes in ethane levels were observed. Pentane and isoprene levels increased significantly after 20 s of breath-holding. Inhalation of purified air before exhalation resulted in a substantial decrease in ethane levels, a moderate decrease in pentane levels and an increase in isoprene levels. CONCLUSION: The major fractions of exhaled ethane, pentane and isoprene seem to be of systemic origin. There was, however, a tendency for ethane to be flow rate dependent in asthmatic subjects, although to a very limited extent, suggesting that small amounts of ethane may be formed in the airways.

Detection of mild emphysema by computed tomography density measurements.

PURPOSE: To assess the ability of a conventional density mask method to detect mild emphysema by high-resolution computed tomography (HRCT); to analyze factors influencing quantification of mild emphysema; and to validate a new algorithm for detection of mild emphysema. MATERIAL AND METHODS: Fifty-five healthy male smokers and 34 never-smokers, 61-62 years of age, were examined. Emphysema was evaluated visually, by the conventional density mask method, and by a new algorithm compensating for the effects of gravity and artifacts due to motion and the reconstruction algorithm. Effects of the reconstruction algorithm, slice thickness, and various threshold levels on the outcome of the density mask area were evaluated. RESULTS: Forty-nine percent of the smokers had mild emphysema. The density mask area was higher the thinner the slice irrespective of the reconstruction algorithm and threshold level. The sharp algorithm resulted in increased density mask area. The new reconstruction algorithm could discriminate between smokers with and those without mild emphysema, whereas the density mask method could not. The diagnostic ability of the new algorithm was dependent on lung level. At about 90% specificity, sensitivity was 65-100% in the apical levels, but low in the rest of the lung. CONCLUSION: The conventional density mask method is inadequate for detecting mild emphysema, while the new algorithm improves the diagnostic ability but is nevertheless still imperfect.

Bronchial mucosal mast cells in asymptomatic smokers relation to structure, lung function and emphysema.

The pathologic mechanisms of chronic obstructive pulmonary disease (COPD) most certainly involves neutrophil granulocytes, cytotoxic T-cells, macophages and mast cells. The aim of this study was to investigate the relation between the number of mast cells in different compartments in bronchial biopsies of central proximal airways to structural changes, lung function tests and emphysema detected by high resolution computed tomography (HRCT). Twenty nine asymptomatic smoking and 16 never-smoking men from a population study were recruited. Central bronchial biopsies were stained to identify mast cells by immunohistochemistry. The number of mast cells in the epithelium, lamina propria and smooth muscle as well as epithelial integrity and thickness of the tenascin and laminin layer were determined. Smokers had increased numbers of mast cells in all compartments (P<0.001). Structural changes were correlated to mast cell numbers with the closest associations to mast cell numbers in the smooth muscle [epithelial integrity (R(S)=-0.48, P=0.008), laminin layer (R(S)=0.63, P=0.0002), tenascin layer (R(S)=0.40, P=0.03)]. Similar correlations between mast cells and lung function tests were seen [functional residual capacity (FRC) (R(S)=0.60, P=0.0006), total lung capacity (TLC) (R(S)=0.44, P=0.02) and residual volume (RV) (R(S)=0.41, P=0.03)]. No correlations could be detected between mast cells and FEV1 or to emphysema. Smoking is associated with an increase of mast cells in all compartments of the bronchial mucosa, including smooth muscle, and this is related to altered airway structure and function.

Effects of abdominal binding on breathing patterns during breathing exercises in persons with tetraplegia.

STUDY DESIGN: Cross-sectional, experimental. OBJECTIVES: To investigate and compare static lung volumes and breathing patterns in persons with a cervical spinal cord lesion during breathing at rest, ordinary deep breathing, positive expiratory pressure (PEP) and inspiratory resistance-positive expiratory pressure (IR-PEP) with and without an abdominal binder (AB). SETTING: The outpatient clinic at the Spinal Unit at Sahlgrenska University Hospital, Goteborg, Sweden. METHOD: The study group consisted of 20 persons with complete cervical cord lesion at C5-C8 level. Breathing patterns and static lung volumes with and without an AB were measured using a body plethysmograph. RESULTS: : With an AB, static lung volumes decreased, vital capacity increased, breathing patterns changed only marginally and functional residual capacity remained unchanged during PEP and IR-PEP. CONCLUSION: Evidence supporting the general use of an AB to prevent respiratory complications by means of respiratory training is questionable. However, the interindividual variation in our results indicates that we cannot rule out that some patients may benefit from the treatment.

High-resolution computed tomography in healthy smokers and never-smokers: a 6-year follow-up study of men born in 1933.

PURPOSE: To elucidate whether emphysematous lesions and other high-resolution computed tomography (HRCT) findings considered associated with smoking are part of a progressive process, and to measure the extent to which similar changes are found in never-smokers. MATERIAL AND METHODS: Healthy smokers and never-smokers were recruited from a randomized epidemiological study and investigated with a 6-year interval. Emphysema, parenchymal and subpleural nodules, ground-glass opacities, bronchial alterations, and septal lines were evaluated in 66 subjects (40 smokers, 11 of whom had stopped smoking in the interval, and 26 never-smokers). Lung function was tested. RESULTS: All except emphysematous lesions were present to some extent in never-smokers. Emphysema, parenchymal nodules, and septal lines occurred significantly more in current smokers, and a progression in extent of emphysema, ground-glass opacities, bronchial alterations and septal lines was seen. There was no significant change among those who stopped and never-smokers except for bronchial alterations, which progressed in never-smokers. CONCLUSION: In healthy, elderly never-smokers a low extent of various HRCT findings has to be considered normal. Emphysema, parenchymal nodules, and ground-glass opacities are indicative of smoking-induced disease. Further progress may cease if smoking is stopped.

Value of air trapping in detection of small airways disease in smokers.

PURPOSE: To test the hypothesis that diffuse and/or focal air trapping are sensitive indicators of airflow obstruction in smoker's small airways disease, when age, gender and presence of emphysematous lesions were allowed for. MATERIAL AND METHODS: Fifty-eight smokers and 34 never smokers, recruited from a randomized population study of men born in 1933, were investigated by HRCT and by extended pulmonary function tests, including a sensitive test for small airways disease (N2 slope). Diffuse air trapping was evaluated by calculating a quotient of mean lung density at expiration and inspiration. Focal air trapping was scored visually by consensus. RESULTS: Diffuse air trapping did not differ between non-emphysematous smokers and never smokers. Furthermore, diffuse air trapping correlated well to the quotient between the residual volume and total lung capacity (RV/TLC, p = 0.01) and was consequently higher in emphysematous smokers than in never smokers. Focal air trapping was found as frequently in smokers without emphysema as in never smokers. Smokers with emphysema showed significantly less focal air trapping. Neither the N2 slope nor any of the other lung function variables differed between those with and without focal air trapping among non-emphysematous smokers. CONCLUSION: Neither diffuse nor focal air trapping are sensitive indicators of smoker's small airways disease.

Evaluation of various attenuation corrections in lung SPECT in healthy subjects.

The effect of increasingly more sophisticated attenuation correction methods on image homogeneity has been studied in seven healthy subjects. The subjects underwent computed tomography (CT), single photon emission computed tomography (SPECT) and transmission computed tomography (TCT) of the thorax region in the supine position. Density maps were obtained from the CT and TCT studies. Attenuation corrections were performed using five different methods: (1) uniform correction using only the body contour; (2) TCT based corrections using the average lung density; (3) TCT based corrections using the pixel density; (4) CT based corrections using average lung density; and (5) CT based corrections using the pixel density. The isolated attenuation effects were assessed on quotient images generated by the division of images obtained using various attenuation correction methods divided by the non-uniform attenuation correction based on CT pixel density (reference method). The homogeneity was calculated as the coefficient of variation of the quotient images (CV(att)), showing the isolated attenuation effects. Values of CV(att) were on average 12.8% without attenuation correction, 10.7% with the uniform correction, 8.1% using TCT map using the average lung density value and 4.8% using CT and average lung density corrections. There are considerable inhomogeneities in lung SPECT slices due to the attenuation effect. After attenuation correction the remaining inhomogeneity is considerable and cannot be explained by statistical noise and camera non-uniformity alone.

On visual determination of full inspiration on CT images.

The aim of this study was to evaluate the ability of experienced thoracic radiologists to assess full inspiration based on two CT slices, one above and one below the carina, in normal subjects. Ten healthy volunteers were studied. Total lung capacity (TLC) was measured with a body plethysmograph. High-resolution computed tomography (HRCT) was performed in two slices at TLC and at various expired volumes. Mean Hounsfield values (HU) were calculated. Unidentifiable images, stored on a web server, were analysed visually by experienced thoracic radiologists. The results show that the mean lung density at TLC varied by approximately 40 HU between individuals. Within an individual this may correspond to a decrease in lung volume of approximately 25% of TLC. On visual determination of images taken at 65-74% of TLC, more than one-third of the images were assessed as taken at full inspiration; of the images taken at 75-84% of TLC, approximately 50% were assessed as taken at full inspiration. We conclude that visual determination of full inspiration on CT images in normal subjects is highly inaccurate. If quantitative density measurements are to be used in the diagnosis or follow-up of lung disease, thorough control of full inspiration is recommended.

Breathing patterns during breathing exercises in persons with tetraplegia.

STUDY DESIGN: Cross-sectional, observational, controlled study. OBJECTIVES: To survey breathing patterns during breathing at rest, ordinary deep breathing (DB), positive expiratory pressure (PEP) and inspiratory resistance-positive expiratory pressure (IR-PEP) among individuals with a cervical spinal cord lesion (SCL) compared with able-bodied controls. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. METHOD: Participants consisted of 20 persons with a complete SCL at the C5-C8 level (at least 1 year postinjury) and 20 matched, able-bodied controls. Breathing patterns and static lung volumes were measured using a body plethysmograph. RESULTS: Compared to the controls, breathing patterns at rest among the people with tetraplegia were characterised by a decreased tidal volume, stable respiratory rate and total cycle duration resulting in decreased mean inspiratory and expiratory flow, and alveolar ventilation. All volume and flow parameters increased except respiratory rate, which decreased during DB and PEP. During IR-PEP, tidal volume increased less compared to PEP, and combined with a decreased respiratory rate the alveolar ventilation was lower than during breathing at rest. The functional residual capacity increased during PEP and IR-PEP in people with tetraplegia. CONCLUSION: DB exercises with or without resistance during expiration or the whole breathing cycle affect the breathing pattern in persons with tetraplegia. DB was superior in increasing volumes and flow. PEP and IR-PEP increased FRC but IR-PEP decreased volumes and flows. However, large interindividual differences in the SCL group indicate the need for caution in generalising the results. SPONSORSHIP: This work was supported in part by grants from the Memorial Foundation of the Swedish Association of registered Physiotherapists and the Association of Cancer and Road Accident Victims.

Quantitative analysis of inhomogeneity in ventilation SPET.

The aim of this study was to evaluate a method for quantification of inhomogeneity in ventilation single-photon emission tomography (SPET). Nine emphysematous patients, nine life-long non-smokers and nine smokers were included in the study. The SPET investigation was performed after 50 MBq (99m)Tc-Technegas had been inhaled by each subject in the supine position. A single-head gamma camera, equipped with a general-purpose parallel-hole collimator using 64 projections (20 s each) over 360 degrees, was used. Data were acquired in 128x128 matrices. Attenuation correction was applied based upon computed tomography (CT) density maps. Lung regions of interest were delineated manually on CT images and then positioned on SPET images. Several attenuation-corrected transaxial SPET slices (thickness 1 cm, spacing 3.5 cm) were reconstructed. Each SPET slice was divided into several 2x2x1 cm(3) elements. Inhomogeneity was assessed by the coefficient of variation (CV) of the pixel counts within these elements (micro-level) and the CV of the total counts of the elements (macro-level). Micro-level CVs in non-smokers varied between 1% and 41%, whereas they were dispersed over a wide range (1%-600%) in emphysematous patients. In seven smokers, the frequency distribution of micro-level CVs was within the normal range, whereas in the other two smokers the values were between the normal range and the range in emphysematous patients. The pooled mean values of micro-level CVs and macro-level CVs in each subject clearly separated the patients from the others. Parametric images of micro-level CV indicated the localisation and severity of ventilation inhomogeneity. We conclude that the present method enables quantification and localisation of regional inhomogeneity in ventilation SPET images.

Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT.

Smoking is a risk factor for developing chronic obstructive pulmonary disease (COPD), but there are no good indicators for early identification of subjects who will develop symptomatic COPD. The aim of this study was to investigate inflammatory mechanisms related to changes in lung function and emphysematous changes on high resolution computed tomography (HRCT) in 'healthy' smokers. Subjects were 60-year-old men from a population study. Bronchoscopy was performed in 30 smokers and 18 who had never smoked. Blood tests, lung function measurements and HRCT were carried out in 58 and 34 subjects, respectively. In comparison with never-smokers, smokers had higher levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP) and lysozyme in blood, higher levels of MPO, interleukin-8 (IL-8) and HNL in bronchial lavage (BL), and of IL-8, HNL and interleukin-lbeta (IL-1beta) in bronchoalveolar lavage (BAL). Smokers also had lower levels of Clara cell protein 16 (CC-16) in blood. HNL in BL and BAL showed strong correlations to other inflammatory markers (MPO, IL-8, IL-1beta). The variations in MPO in BL were explained by variations in HNL (R2 =0.69), while these variations in BAL were explained by variations in HNL and IL-1beta (R2 = 0.76). DL(CO) was the lung function variable most closely related to MPO and IL-8 in BL and BAL and to IL-1beta in BAL. In a multiple regression analysis, MPO, IL-1beta, IL-8 and CC-16 in BL and MPO in BAL contributed to the explanation of variations in DL(CO) to 41% and 22%. respectively, independent of smoking habits. In smokers with emphysematous lesions on HRCT, HNL in BAL correlated to emphysema score (r(s) = 0.71). We conclude that 'healthy' smoking men with a near normal FEV1 show signs of inflammation in the lower airways that are related to a decrease in DL(CO) and to emphysematous lesions on HRCT. This inflammation seems to be the result of both monocyte/macrophage and neutrophil activation.

Nasal airflow patterns during the velopharyngeal closing phase in speech in children with and without cleft palate.

OBJECTIVES: (1) To study the nasal airflow patterns during the velopharyngeal closing phase in speech produced by children with and without cleft palate. (2) To compare the nasal airflow patterns in bilabial, dental, and velar articulation in these children. DESIGN: Prospective, cross-sectional study of a consecutive series of children with cleft palate referred for routine speech evaluation and controls. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: Seventeen children with cleft lip and palate or cleft palate only and 22 controls aged 7 and 10 years. METHOD: Nasal airflow was transduced with a pneumotachograph attached to a nose mask and registered together with the acoustic speech signal. Sentences containing nasal-to-stop combinations in bilabial, dental, and velar articulatory positions were used. MAIN OUTCOMES MEASURES: The duration from peak to 5% nasal airflow, the maximum flow declination rate, and the nasal airflow at selected points in time during the transition from nasal-to-stop consonants. RESULTS: In the cleft palate group, duration from peak to 5% nasal airflow was clearly longer than among the controls (p <.0001). The declination of airflow was slower (p <.006) and the rate of nasal airflow at the release of the stop consonant was higher (p <.004) in the cleft palate group. Differences between bilabial versus dental and velar articulation were found in the control group. CONCLUSION: Studies of the temporal and dynamic characteristics of the nasal airflow variations during speech appear potentially useful for the assessment of velopharyngeal function.

Dynamics of 'Technegas' deposited in the lung.

In tomographic Technegas ventilation studies, the deposited aerosol should be stable. The aim of this study was to investigate the stability of deposited Technegas in severely obstructed patients and in healthy volunteers. Six emphysematous patients and five healthy volunteers were studied. Anterioposterior (AP) and posterioanterior (PA) dynamic images of ventilation (120 frames, 1 frame.min-1) were acquired after inhalation of 99mTc-Technegas' in the supine position. The time-activity curve of the whole lung showed two phases in the emphysematous patients as well as in the healthy volunteers. The activity decreased rapidly in the first phase, then reached almost a constant level (the second phase) after approximately 50 min. The logarithms of both the first phase and the second phase were close to straight lines. The half-time of the first phase was approximately 9 min. No systematic differences in 'Technegas' clearance rate were found between central regions and peripheral regions and between high count rate regions and normal count rate regions. Pertechnegas contamination was subsequently detected, and we conclude that the rapid first phase is probably due to clearance of Pertechnegas. When stable Technegas is required, we suggest that data acquisition should start about 50 min after inhalation.

Respiratory symptoms relate to physiological changes and inflammatory markers reflecting central but not peripheral airways. A study in 60-year-old 'healthy' smokers and never-smokers.

The aim of this study was to evaluate the relationship between respiratory symptoms, lung function and inflammatory markers in 'healthy' smokers. The study population was recruited from an epidemiological study with subjects of the same age, 60 years. Only smokers who considered themselves healthy (n=58) and a random sample of never-smokers (n=34) were investigated. All subjects underwent lung function tests--spirometry, carbon monoxide transfer (DLco) and the single-breath N2 method (N2 test)--together with high-resolution computed tomography (HRCT). A flexible bronchoscopy with a bronchoalveolar lavage (BAL) was performed in 30 smokers and 18 never-smokers. Bronchial biopsies were also taken. Smokers who reported non-specific respiratory problems, chronic bronchitis and wheezing in a symptom questionnaire had a lower forced expiratory volume in 1 sec (FEV1), FEV% and specific airway conductance (sGaw), lung function tests supposed to reflect the more central airways, than smokers without respiratory symptoms. A limited number of smokers with occasional non-specific respiratory problems also had more cytotoxic T cells (CD8) in bronchial biopsies. No differences were found in DLCO and the N2 test, lung function tests supposed to reflect the more peripheral airways including the alveoli, HRCT-diagnosed emphysema or inflammatory markers in blood and BAL between smokers with and without respiratory symptoms. It is concluded that even when smokers consider themselves 'healthy' they have mild symptoms that are related more to physiological changes and inflammatory markers that may reflect events in the central airways than to changes that may reflect events in the peripheral airways.

End-tidal to arterial oxygen tension difference as an oxygenation index.

BACKGROUND: "Ideal" alveolar oxygen tension (PAO2) is a calculated entity and the alveolar-arterial oxygen tension difference (PA-aO2) is used to evaluate gas exchange function of the lungs. Accurate calculations of PAO2 necessitate measurements of the respiratory exchange ratio (RER), which is less frequently done, and most often approximations are made. The measured end-tidal oxygen tension (PETO2) is a reflection of the alveolar oxygen tension. The aim was to study the relationship between PAO2 and PETO2, and to see whether the end-tidal to arterial oxygen tension difference (PET-aO2) could give the same information about lung function as PA-aO2. METHODS: Twenty patients admitted for cardio-pulmonary exercise tests were studied. They bicycled for 4 min at each work load until maximum work load was reached. Arterial blood gases were analysed before, after 4 min at each work load, at maximum work load and after 2 min of recovery. A metabolic computer measured mixed expired gas concentrations. End-tidal gas concentrations were measured with a side stream gas analyser. RESULTS: We measured major increases in oxygen uptake, carbon dioxide elimination and RER. PAO2 and PETO2 increased at maximum exercise and during recovery. PAO2 and PETO2 were closely correlated during the study, through great changes in oxygen uptake and RER (r=0.88). When correction was made for wet gas the median difference was 0.12 kPa. CONCLUSIONS: At ambient air (FIO2=0.21), PET-aO2 as a respiratory index may give equivalent information to PA-aO2, without the need for measurements of mixed expired gas tensions or the hazard of an assumed RER.

Nasobronchial relationship after cold air provocation.

Provocation with cold air in the nose causes broncho-obstruction while warm air causes bronchodilation in patients with asthma, but not in healthy subjects. These findings have suggested the existence of a nasobronchial reflex. The present study aimed to block this effect and evaluate the mechanisms underlying the effect on lung function after cold stimulation of the nose. Lung function, as measured with specific conductance and forced expiratory flow, was reduced after cold stimulation of the nose, but this effect could not be blocked by anesthetizing the nose or by inhaling an anti-cholinergic drug before the provocation. These results confirm the presence of a nasobronchial relationship, but not of a nasobronchial reflex.

Effect of nasal air temperature on FEV1 and specific airways conductance.

We investigated whether changes in nasal air temperature affect specific airway conductance (SGaw) and one second forced expiratory volume (FEV1) in 10 asthmatic patients with a history of cold-sensitive asthma and eight healthy subjects. An air-stream (0.6 l s-1) of -15 degrees C, +22 degrees C or +37 degrees C was blown into both nostrils during a Valsalva manoeuvre. Each provocation consisted of 10 puffs of air, each of 15 s duration, at 1 min intervals. Before and at regular intervals after the provocations, SGaw and FEV1 were determined. In asthmatics, after cold air provocation, SGaw fell 23% (P<0.01) and FEV1 8% (P<0.01). After the warm air provocations, SGaw rose 15% (P<0.01) and FEV1 6% (P<0.01). After the ambient air provocations, no significant changes occurred in SGaw or FEV1. In the healthy subjects, the nasal provocations caused no significant changes in lung function. The present study shows that cold air in the nose causes a slight obstruction and warm air possibly a slight dilatation of the lower airways in patients with a history of cold-sensitive asthma but not in healthy subjects.