Early changes of respiratory function in mitral valve stenosis

In order to detect early changes of respiratory function in patients affects by pure mitral valve stenosis, the authors selected 12 patients-non smokers, without symptoms of respiratory disease, of I and II NYHA class. In all subjects right and left cardiac catheterization and conventional spirometric measurements were performed. Then maximal mid-expiratory flow (MMEF), maximal expiratory flow at 50% of vital capacity (MEF 50%), maximal expiratory flow at 25% of vital capacity (MEF 25%), closing volume (CV) and closing capacity (CC) were determined, to find a small airways (bronchi of caliber inferior to 2 mm) disease. Whereas conventional spirometric measurements showed normal values, the small airways disease was proved by MEF 50% and MEF 25% measurements. The small airways obstruction observed by the authors may be due to: a) dilatation of pulmonary vessels because of venous congestion resulting in the compression of adjacent small airways; b) partial bronchiolar obstruction because of congestion of submucous venous plexus; c) interstitial oedema due to increase of extravascular pulmonary water because of pulmonary venous congestion.     

Bronchial airway deposition and retention of particles in inhaled boluses: effect of anatomic dead space

The fractional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the relative volume and size of an individual's airways. To evaluate the effect of variable anatomic dead space (ADS) on aerosol bolus delivery we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5 micron mean mondispersed aerosol diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at a lung volume of 70% total lung capacity end inhalation. By using filter techniques, aerosol photometry, and gamma camera analysis, we estimated the fraction of the inhaled boluses deposited in intrathoracic airways (IDF). ADS by single-breath N2 washout was also measured from 70% total lung capacity. Results showed that among all subjects IDF was variable (range = 0.04-0.43, coefficient of variation = 0.54) and increased with decreasing ADS (r = -0.76, P = 0.001, n = 16). We found significantly greater deposition in the left (L) vs. right (R) lungs; mean L/R (ratio of deposition in L lung to R lung, normalized to ratio of L-to-R lung volume) was 1.58 +/- 0.42 (SD; P < 0.001 for comparison with 1.0). Retention of deposited particles at 2 h was independent of ADS or IDF. There was significant retention of particles at 24 h postdeposition (0.27 +/- 0.05) and slow clearance of these particles continued through 48 h postdeposition. Finally, analysis of central-to-peripheral ratios of initial deposition and 24-h-retention gamma-camera images suggest significant retention of insoluble particles in large bronchial airways at 24 h postdeposition (i.e., 24 h central-to-peripheral ratio = 1.40 +/- 0. 44 and 1.82 +/- 0.54 in the R and L lung, respectively; P < 0.02 for comparison with 1.0). These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.     

Small airways dimensions in asthma and in chronic obstructive pulmonary disease

The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of DNA damage recovery processes in the adaptive response to ionizing radiation in human lymphocytes

Size-dependent structural patterns in the conductive bronchial tree of four species of myomorph rodents of different body weight were determined by lung casts. The lungs of the harvest mouse, Micromys minutus, body weight 5-7 g, the house mouse, Mus musculus, body weight 35-45 g, the brown rat, Rattus norvegicus, body weight 200-400 g, and the African giant pouched rat, Cricetomys gambianus, body weight 1,200-1,800 g, were inflated to 20 cm H2O, frozen, freeze-dried, hardened, and filled with silicone rubber. The casts were pruned, and branching pattern, diameter, and volume of the conductive bronchial tree were determined using a binocular magnifier. All four species have four lobes on the right lung and an undivided left lung, and the central bronchial tree on either side shows an identical monopodial branching pattern. Although the ramification of the central conductive bronchi is not size-dependent, the diameter and volume are. The diameter of the left main bronchus equals 1.24% of body length in Micromys and 0.6% in Cricetomys, and the conductive bronchial tree makes up 13% of the total lung volume in Micromys and 6% in Cricetomys. Relatively wider airways and a decline in airway resistance with declining body mass in small mammals compared to large ones result in a high ventilatory dead space, which is compensated for by a higher breathing frequency.     

Is it possible to predict the result of the bronchial provocation test in children with asthma?

Bronchial hyperreactivity (BHR) to different allergic and non-allergic stimuli is characteristic feature of asthma. Sometimes however it is not possible to perform bronchial provocation test (BPT) assessing reactivity. It was interesting for us if the result of BPT can be predicted on the base of routine lung tests. The aim of the study is evaluation of the relationship between BPT results and baseline lung function tests assessing small bronchi obstruction in children suffering from asthma. Investigated group comprised 139 children aged 7 to 17 years, with episodic, mild or moderate asthma. During bronchial challenge lung function was assessed on the base of spirography and maximal flows at 50% and 25% of forced vital capacity (MEF50 and MEF25) and other indices as surface under end-half of flow-volume curve and mean flow times T50 and T25. The study results confirmed good correlation between BPT result and baseline lung function. Those children which had worse initial lung tests had more pronounced bronchial hyperreactivity. This relationship was the closest in the group of children with small bronchi obstruction. Analysis of correlation showed highly significant relationship between baseline lung function tests and degree of bronchial reactivity. The highest significance was observed for MEF50 and MEF25. We conclude that small bronchi test disturbances in children with asthma could predict with high probability results of bronchial challenge.     

Morphological investigation of the neonatal lung with respiratory distress syndrome which was maximally distended with Somentor 33 and formalin (author's transl)]

The importance of morphological immaturity of the lung in the development of the respiratory distress syndrome was investigated. Atelectatic lungs of newborns were maximally expanded with a mineral oil of low kinematic viscosity (Somentor 33) or 10% Formalin. With this method, surface active forces of peripheral air spaces should not impede expansion of the lungs. 27 lungs of neonates who died of respiratory distress syndrome and 10 lungs of neonates without primary respiratory problems were examined. Following maximal expansion of the lungs with the respiratory distress syndrome show a hypercellular densely cellular tissue of the pulmonary segments, much like glanduloid hyperplasia with small peripheral air spaces and long distances for diffusion of the respiratory gases. The lungs of newborns without respiratory distress syndromes are well alveolar following expansion and show an optimal morphology for gas diffusion. A lack of a surfactant should have significant consequences in small air spaces.     

Bronchial adenoma resection with relief of hypoxic pulmonary vasoconstriction

Experimental airway obstruction is known to cause reflex pulmonary artery constriction, but clinical documentation of reversible bronchial obstruction and vasoconstriction is rare. A soft bronchial adenoma obstructed the left main bronchus, and scans showed minimal ventilation and perfusion on the left. Gas aspirated from beyond the tumor was hypoxic. The adenoma was removed and the lung left intact by means of a skin graft in the bronchial wall. Four months later, pulmonary function was normal, and both ventilation and perfusion of the left lung were normal. Reflex pulmonary vasoconstriction resulting from alveolar hypoxia minimizes systemic hypoxemia and also minimizes alveolar tissue hypoxia in the lung itself. The reflex is seen most frequently in perfusion scans in patients with chronic airways disease. This case in important in that it documents reversal of vasoconstriction after ventilation was restored.     

Efficiency of airway macrophage recovery by bronchoalveolar lavage in hamsters: a stereological approach

Macrophages play a central role in the defence of the respiratory tract against deposited particles. In addition to the well-studied alveolar macrophages, airway macrophages have been recognized as an important clearance factor. Bronchoalveolar lavage (BAL) has been used for functional and morphological investigations of macrophages in vitro, assuming that all macrophages are removed with equal probability from the lung surface. Airway macrophages have been found in close contact with the epithelial cells. These macrophages may not be easily removed by lavage, and they might constitute a functionally different macrophage population. We have tested the hypothesis that there exists a population of macrophages in the conducting airways that resists removal by lavage. We lavaged the lungs of four hamsters and fixed the lungs, thereafter, by intravascular perfusion. The number of macrophages in the intrapulmonary conducting airways was estimated with an unbiased stereological technique, the fractionator, and compared to the number of macrophages in the airways of four hamsters whose lungs had not been lavaged prior to fixation. This in situ study revealed that, in hamster lungs, 42% of the airway macrophages were not removed by BAL and that about 5% of all macrophages in the BAL fluid were airway macrophages. Additionally, ultrastructural alterations of the airway epithelium were found. It is concluded that there exists a population of airway macrophages that resists lavage. This is an aspect which has to be considered in studies performed with macrophages obtained by BAL, since they could represent a functionally different macrophage population.     

Spectrophotometric determination of methoxamine using cerium(IV) in presence of sodium lauryl sulphate and rhodamine-B

Several lines of evidence suggest that the responsiveness of the airways is heterogeneous, although the magnitude of this heterogeneity has not been quantified. We have developed a videomicroscopic method that allows the measurements of the responsiveness of individual explanted airways to contractile agonists such as methacholine. Liquid agarose at 37 degrees C is injected into human lung segments to inflate them to a volume equivalent to total lung capacity. The agarose-filled lungs are then gelled by brief refrigeration and 0.5-mm-thick explants prepared by sectioning. The explants are cultured overnight under conventional conditions. Sections with airways cut in cross section are identified and placed on an inverted videomicroscope. Airway lumen area is then measured following administration of methacholine in increasing concentrations, permitting the construction of dose-response curves for each airway segment studied. This system thus lends itself to the study of the heterogeneity of airway responsiveness across the airway tree by permitting the study of distributions of airways. Using this approach, we have observed a very high degree of heterogeneity of responsiveness across the airways of human lungs. In this report, we review these findings and discuss the physiologic implications of heterogeneity.     

Effect of ventilation on movement of surfactant in airways

The effect of ventilation on movement of surfactant in airways was studied in rat lungs. Male albino rats were anesthetized and sacrificed by exsanguination. The trachea was cannulated and the diaphragm opened to allow the lungs to collapse. The lungs were left in chest and kept at minimal volume, or at constant inflation with air, or were ventilated with air, nitrogen or oxygen. At the end of 3 hr the extrapulmonary airways (EPA), i.e. trachea and bronchi, were separated from the lungs and flushed with 40 ml isotonic saline. The surface tension and lecithin content of the saline wash was then measured. The surface activity and lecithin content of the EPA wash did not change if the lungs were kept at minimal volume or at constant inflation, but increased following ventilation. This increase was directly related to the duration of ventilation and to the tidal volume and inversely related to the end-expiratory pressure. It was independent of O2 concentration of the gas used for ventilation. The results suggest that ventilation enhances the movement of surfactant in airways and that positive end-expiratory pressure prevents this effect of ventilation.     

Long-term effect of coal and rock dust on the changes of some biochemical parameters in miners

The study revealed those changes in connective tissue components and validity of alveolar macrophages in bronchial lavage, which were in correlation with duration and severity of exposure to coal and rock dust. The data proved that roentgenologio changes in the lungs are preceded by changed quantity of viable alveolar cells, higher content of hexauronic acids and hexoses associated with proteins. The stated biochemical tests could be applied to early diagnosis in individuals prone to pneumoconiosis.     

Certification and occupational health nursing. An historical perspective

BACKGROUND: The bronchodilator agent is an important drug for patients with chronic obstructive pulmonary disease. Methacholine is a popular bronchial provocative agent. Although the major acting site of bronchodilator, methacholine and upper respiratory tract infection (URI) has been evaluated in some studies, the sites are still in debate. This study investigated the exact major acting sites. METHODS: Thirty subjects participated in this study. Episodes of URI were identified by a questionnaire. Spirometry, bronchial provocative test with methacholine, and five minutes' inhalation of a mixture of helium and oxygen (HeO2) were done on day one. Spirometry, bronchodilator test, with five minutes' inhalation of HeO2 and expiratory flow-volume (F-V) curve were performed on another day. The change of pre- and post-HeO2 VEMax50 was calculated as delta VEMax50. The pre- and post-bronchodilator VEMax50 and delta VEMax50 differences were counted to decide the acting site of bronchodilator. After bronchial provocative test with methacholine, the volume of isoflow (VisoV) was estimated from pre- and post-HeO2 F-V curve to establish the acting site of methacholine. RESULTS: This study indicated that small airways are the major acting sites of bronchodilators, large airways are the major acting sites of methacholine and URI affects mainly large airways. Although airway hyperresponsiveness is more severe in subjects with positive methacholine response, the recovery of spirometry values is not significantly different between the methacholine-positive and -negative groups. CONCLUSIONS: The major acting sites of the bronchodilator, methacholine, and URI are the small, large and large airways, respectively. Bronchial hyperresponsiveness is not a cause of quick restoration of spirometry values in subjects with positive methacholine response.     

Recognition of normal, neoplastic, and fetal airway epithelial cell membranes by two monoclonal antibodies

The reactivity of two rat monoclonal antibodies was studied. These antibodies, A2R and A2C, bind a 32 kDa alveolar type II cell membrane receptor for surfactant protein A. A2R and A2C also bind apical cell membranes of ciliated and nonciliated cells of the conducting airways. Because this reactivity suggested possible utility in targeting those cells for therapeutic gene transfer, the binding activity of these two antibodies was examined in human tissues. In conducting airways, A2R and A2C bound apical epithelial cell membranes throughout the embryologic period studied: from 15 weeks of gestation, through maturity. Reactivity was more restricted to ciliated cells of the airways as maturation progressed. In the peripheral lung, A2C and A2R only bound most cells in the early developing lung, but mainly type II cells in mature lungs. Other normal tissues recognized by these antibodies included crypt lining cells of the adult and fetal stomach, large bile duct epithelium, and pancreatic acinar cells. All of these cells derive from embryonic foregut endoderm. Other normal tissues, both of endodermal and nonendodermal origin, were negative. Pulmonary carcinomas were studied. A2C and A2R recognized all non-small cell carcinomas of the lung tested. In contrast, none of the small cell carcinomas or carcinoid tumors of the lung were recognized by these antibodies. The function of p32 in these diverse cell types is not clear, but whatever its role in these tissues, antibodies versus p32 may potentially be used to target gene or drug therapy to the normal or malignant cells they recognize.     

The effect of maternal restraint on developmental toxicity of aluminum in mice

We have estimated lung volume, bronchial volume, vessel volume, alveolar surface area and capillary length in patients who died of lung failure due to emphysema and chronic obstructive pulmonary disease (COPD) and in patients with no clinical signs of respiratory disease. Unbiased morphometric methods were applied to the right lung. The patients with emphysema had equal lung volumes and bronchial and vessel volumes compared to the control group. The alveolar surface area and surface density were significantly decreased to about 67%, of control values. The capillary length and length density were significantly decreased to about 68% of control values. The proportional decreases in alveolar surface area and capillary length suggest that compensatory capillary proliferation has not occurred. These unbiased morphometric studies of emphysema have yielded results in end-stage emphysema that are comparable to those previously reported using biased methods. However, the unbiased methods may provide new insights when applied to earlier stages of the disease.     

Bronchial reactivity, lung function, and serum immunoglobulin E in smoking-discordant monozygotic twins

Smokers with chronic bronchitis and/or chronic obstructive pulmonary disease (COPD) have been reported to have an increased bronchial reactivity (BR). It has been discussed whether increased BR is a risk factor for the development of COPD in smokers. We studied 10 monozygotic twin pairs who were discordant for tobacco smoking by means of histamine provocation tests, lung function tests, and serum samples for total IgE. The smokers had a mild obstructive ventilatory impairment, with FEV1 significantly lower than that of the partner both when it was determined from the flow-volume loops (3.2 +/- 1.0 L for smokers and 3.4 +/- 0.8 L for nonsmokers) and by the Vitalograph spirometer (3.5 +/- 1.0 L for smokers and 3.8 +/- 0.8 L for nonsmokers). Forced midexpiratory flow (FEF25-75%) and forced expiratory flow at 75 to 85% of vital capacity (FEF75-85%) were both significantly lower in the smokers (p < 0.05). The alveolar plateau phase N2-delta test and lung clearing index in the multibreath nitrogen washout test were both significantly affected in the smokers (p < 0.05 and p < 0.01, respectively). We found no significant difference in histamine reactivity between smokers and nonsmokers and no correlation between differences in reactivity and differences in lung function within pairs. Total serum IgE was significantly higher in the smokers than in their nonsmoking siblings. These data suggest that obstructive ventilatory impairment and raised serum IgE are earlier and more constant manifestations of tobacco smoking than increased bronchial reactivity. Thus, bronchial hyperreactivity does not seem to be a major risk factor for the development of early airways obstruction in smokers.     

Intravascular volume loading reversibly decreases airway cross-sectional area

High-resolution computed tomography was used to directly determine the short-term effects of intravascular volume expansion on airway caliber. The change in airway cross-sectional area caused by intravascular volume expansion (30 ml/kg, Ringer's lactate) was studied in six anesthetized mini-pigs within 5 min. Twenty-five of 27 large airways (diameter, 2.01 to 5.0 mm) demonstrated decreased internal cross-sectional area (10.56 +/- 1.26 vs 8.66 +/- 1.03 mm2, p < 0.001). Twenty of 24 small airways (diameter, 0.75 to 2.0 mm) showed decreased internal cross-sectional area (1.82 +/- 0.16 vs 1.44 +/- 0.16 mm2, p < 0.001). These changes were rapidly (< 6 min) reversed by intravascular volume reduction. The external airway cross-sectional area did not change. These data suggest rapid, reversible bronchial mucosal vascular engorgement as a cause of increased airway resistance in heart failure.     

The alveolar surface network: a new anatomy and its physiological significance

It is generally held that the terminal lung unit (TLU) is an agglomeration of alveoli that opens into the branching air spaces of respiratory bronchioles, alveolar ducts, and alveolar sacs and that these structures are covered by a continuous thin liquid layer bearing a monomolecular film of surfactants at the open gas-liquid interface. The inherent structural and functional instability given TLUs by a broad liquid surface layer of this nature has been mitigated by the discovery that the TLU surface is in fact an agglomeration of bubbles, a foam (the alveolar surface network) that fills the TLU space and forms ultrathin foam films that 1) impart infrastructural stability to sustain aeration, 2) modulate circulation of surface liquid, both in series and in parallel, throughout the TLU and between TLUs and the liquid surface of conducting airways, 3) modulate surface liquid volume and exchange with interstitial liquid, and 4) sustain gas transfer between conducting airways and pulmonary capillaries throughout the respiratory cycle. The experimental evidence, from discovery to the present, is addressed in this report. Lungs were examined in thorax by stereomicroscopy immediately from the in vivo state at volumes ranging from functional residual capacity to maximal volume (Vmax). Lungs were then excised; bubble topography of all anterior and anterolateral surfaces was reaffirmed and also confirmed for all posterior and posterolateral surfaces. The following additional criteria verify the ubiquitous presence of normal intraalveolar bubbles. 1) Bubbles are absent in conducting airways. 2) Bubbles are stable and stationary in TLUs but can be moved individually by gentle microprobe pressure. 3) Adjoining bubbles move into the external medium through subpleural microincisions; there is no free gas, and vacated spaces are rendered airless. Adjacent bubbles may shift position in situ, while more distal bubbles remain stationary. 4) The position and movement of "large" bubbles identifies them as intraductal bubbles. 5) Transection of the lung reveals analogous bubble occurrence and history in central lung regions. 6) Bubbles become fixed in place and change shape when the lung is dried in air; the original shape and movement are restored when the lung is rewet. 7) All exteriorized bubbles are stable with lamellar (film) surface tension near zero. 8) Intact lungs prepared and processed by the new double-embedding technique reveal the intact TLU bubbles and bubble films. Lungs were also monitored directly by stereomicroscopy to establish their presence, transformations, and apparent function from birth through adulthood, as summarized in the following section. ANATOMY: Intraalveolar bubbles and bubble films (the unit structures of the alveolar surface network) have been found in all mammalian species examined to date, including lambs, kids, and rabbit pups and adult mice, rats, rabbits, cats, and pigs. Rabbits were used for the definitive studies. 1) A unit bubble occupies each alveolus and branching airway of the TLU; unit bubbles in clusters correspond with alveolar clusters. 2) The appositions of unit bubble lamellae (films) form a network of liquid channels within the TLUs. The appositions are bubble to bubble (near alveolar entrances, at pores of Kohn, and between ductal bubbles), bubble to epithelial cell surface, and bubble to surface liquid of conducting airways. They rapidly form stable Newtonian black foam films (approximately 7 nm thick) under hydrodynamic conditions expected in vivo. 3) Lamellae of the foam films and bubbles tend to exclude bulk liquid and thus maintain near-zero surface tension. At the same time, the foam film formations--abetted by the constant but small retractive force of tissue recoil--stabilize unit bubble position within the network. 4) Unit bubble mobility in response to applied force increases as liquid accumulates within the network (e.g. (ABSTRACT TRUNCATED)     

Inflammatory cell distribution within and along asthmatic airways

Asthmatic airways are infiltrated with inflammatory cells that release mediators and cytokines into the microenvironment. In this study, we evaluated the distribution of CD45-positive leukocytes and eosinophils in lung tissue from five patients who died with severe asthma compared with five patients with cystic fibrosis. For morphometric analysis, the airway wall was partitioned into an "inner" area (between basement membrane and smooth muscle) and an "outer" area (between smooth muscle and alveolar attachments). Large airways (with a perimeter greater than 3.0 mm) from patients with asthma or cystic fibrosis had a greater density of CD45-positive cells (p < 0.05) and eosinophils (p < 0.001) in the inner airway region compared with the same airway region in small airways. Furthermore, in small airways, asthmatic lungs showed a greater density of CD45-positive cells (p < 0.01) and eosinophils (p < 0.01) in the outer compared with the inner airway wall region. These observations indicate that there are regional variations in inflammatory cell distribution within the airway wall in patients with asthma that are not observed in airways from patients with cystic fibrosis. We speculate that this inflammatory cell density in peripheral airways in severe asthma may relate to the peripheral airway obstruction characteristic of this condition.     

Single-exhalation profiles of NO and CO2 in humans: effect of dynamically changing flow rate

Endogenous production of nitric oxide (NO) in the human lungs has many important pathophysiological roles and can be detected in the exhaled breath. An understanding of the factors that dictate the shape of the NO exhalation profile is fundamental to our understanding of normal and diseased lung function. We collected single-exhalation profiles of NO and CO2 from normal human subjects after inhalation of ambient air (approximately 15 parts/billion) and examined the effect of a 15-s breath hold and exhalation flow rate (VE) on the following features of the NO profile: 1) series dead space, 2) average concentration in phase III with respect to time and volume, 3) normalized slope of phase III with respect to time and volume, and 4) elimination rate at end exhalation. The dead space is approximately 50% smaller for NO than for CO2 and is substantially reduced after a breath hold. The concentration of exhaled NO is inversely related to VE, but the average NO concentration with respect to time has a stronger inverse relationship than that with respect to volume. The normalized slope of phase III NO with respect to time and that with respect to volume are negative at a constant VE but can be made to change signs if the flow rate continuously decreases during the exhalation. In addition, NO elimination at end exhalation vs. VE produces a nonzero intercept and slope that are subject dependent and can be used to quantitate the relative contribution of the airways and the alveoli to exhaled NO. We conclude that exhaled NO has an airway and an alveolar source.     

13-cis-retinoic acid or all-trans-retinoic acid plus interferon-alpha in recurrent cervical cancer: a Southwest Oncology Group phase II randomized trial

BACKGROUND: Although previous studies have established the presence of an eosinophil-rich cellular infiltrate in the small airways of asthmatic lungs, the expression of cytokines within the peripheral airways has been largely unexplored. The purpose of our study was to test the hypothesis that TH2-type cytokines are increased in the peripheral airways and parenchyma of asthmatic lungs. METHODS: The presence of messenger ribonucleic acid (mRNA) encoding both T-helper (TH1)-type (IL-2, interferon-gamma) and TH2-type (IL-4, IL-5) cytokines in surgically resected lungs from six asthmatic and 10 nonasthmatic subjects was determined by in situ hybridization. Colocalization of IL-5 mRNA within the large and small airways was performed by simultaneous in situ hybridization and immunocytochemistry. RESULTS: Expression of IL-5 mRNA-positive cells was significantly increased in the large and small airways and in the lung parenchyma of asthmatic subjects compared with nonasthmatic subjects. In the asthmatic individuals, the expression of IL-5 mRNA was increased in the small airways compared with the large airways. There was also an increase in the number of cells expressing IL-4 mRNA in the large and small asthmatic airways compared with the nonasthmatic airways. In contrast, the numbers of IL-2 and interferon-gamma mRNA-positive cells did not differ between asthmatic and nonasthmatic individuals. CONCLUSIONS: We conclude that there is an increased expression of TH2-type cytokines within the peripheral airways of asthmatic lungs and suggest that the small airways contribute to the pathophysiology of asthma.