Tobacco smoking is associated with increased prevalence of various diseases, both in the respiratory tract and in distal organs. The possibility that tobacco smoke induced changes in immune and inflammatory processes may play a part in the aetiology and pathogenesis of many of these diseases was first recognised in the mid 1960s. The ensuing decade witnessed a steadily increasing research effort centred on toxicological aspects of chronic inhalation of tobacco smoke in relation to immune and inflammatory cell function in experimental animals. This work (reviewed by Holt and Keast') defined a discrete pattern of change in animals during the course of tobacco smoke exposure, with the following salient features: (1) systemically, biphasic fluctuations were observed in primary T cell dependent humoral and cellular immune responses, initial enhancement during the first few months of exposure eventually giving way to suppression in chronically exposed animals; (2) T cell independent immune responses (for example, to bacterial polysaccharide antigens) and secondary immune responses dependent on T memory cells remained normal in these animals; (3) an immediate and profound suppression of T cell function was noted in the respiratory tract, together with (4) the steady development of an expanded and functionally altered population of alveolar macrophages. Recognition of the possibility that similar effects occur in man has provided the impetus for various direct studies on aspects of immune and inflammatory cell functions in human smokers. Furthermore, it has become accepted practice to segregate the smokers within \"control\" populations, particularly in studies using bronchoalveolar lavage. The available data from these human studies are reviewed below in the light of the information available from earlier animal experiments.

https://thorax.bmj.com/content/thoraxjnl/42/4/241.full.pdf

Immune and inflammatory function in cigarette smokers.

Bronchoalveolar lavage (BAL) is increasingly used in the assessment of pulmonary diseases in children. However, reference values for cellular and non-cellular constituents of BAL fluid in children are lacking. We have studied the differential cytology of BAL fluid in 48 children aged 3-16 years (mean age +/- SD 7.9 +/- 3.5 yrs) undergoing elective surgery for nonpulmonary illnesses. A flexible bronchoscope (Pentax 3.5 or 4.9 mm) was wedged in the middle lobe or one of its segments. BAL was performed with 3x1 ml-kg-1 body weight of normal saline warmed to body temperature. The first sample was studied separately; subsequent samples were pooled for analysis. The mean recovery was 58 +/- 15%. Significantly more granulocytes and less lymphocytes were found in the first, as compared to the pooled, sample. Total cell counts were highly variable and ranged from 0.5-57.1 x 10(4) ml-1. Macrophages were the predominant cell type, with a mean percentage of 81.2 +/- 12.7%. The relative proportion of lymphocytes was higher than that reported in most studies of adult volunteers (16.1 +/- 2.4%). No age dependency was observed for either cell type. The mean percentage of granulocytes was 2.5 +/- 3.3%. Absolute granulocyte counts were significantly higher in children under 8 yrs of age. This study provides the first reference data on BAL differential cytology in children without pulmonary disease and will be the basis for future investigations of BAL in paediatric lung diseases.

https://erj.ersjournals.com/content/erj/7/10/1865.full.pdf

Differential cytology of bronchoalveolar lavage fluid in normal children

Bronchoalveolar lavage (BAL) is used to obtain inflammatory cells from the lung. for clinical research, parametric statistics are frequently used to compare cells present in BAL of patients with lung disease with cells present in BAL of normal subjects. To determine if these populations can be compared in this manner we performed BAL on 111 never-smoking, normal volunteers and determined: (1) the mean, median, standard deviation, and range of the cells in BAL; (2) whether the data are normally distributed and satisfy the criteria for use of parametric statistical analysis. The BAL cellularity was expressed as a percentage of total cells, cells per milliliter return, and total cells per lavage. Regardless of the means of expression, no measure of BAL cellularity (total cells, macrophages, lymphocytes, neutrophils, or eosinophils) conformed to the normal (bell-shaped) distribution when tested for goodness of fit with the G statistic (all p < 0.001). The lack of fit to the normal distribution was not substan...

Bronchoalveolar lavage cellularity. The distribution in normal volunteers.

Cigarette smoking influences the risk of orogastrointestinal disease in both protective (ulcerative colitis), and inductive (squamous tumours of the head, neck and oesophagus) roles. In order to study the effects of smoking on mucosal immunity, salivary immunoglobulins were measured in pure parotid saliva from groups of healthy non-smokers, smokers, and exsmokers and from patients with epithelial head and neck tumours, both untreated and after radiotherapy. Of the healthy individuals, smokers had significantly lower salivary IgA and higher IgM concentrations than did non-smokers. The effect on IgA was dose related, and reversible after cessation of smoking. Likewise, in patients with head and neck tumours (the majority being smokers), salivary IgA concentration was reduced and IgM increased when compared with non-smoking controls. Results were similar before and after radiotherapy. This study provides evidence of the effects of smoking on mucosal immunity as evaluated by parotid salivary immunoglobulins. Further studies of the influence of smoking on secretory immunity are indicated.

https://gut.bmj.com/content/gutjnl/31/4/378.full.pdf

Mucosal immunodeficiency in smokers, and in patients with epithelial head and neck tumours.

We evaluated bronchoalveolar lavage fluid (BAL) for cellular constituents, concentration of total protein (TP), albumin (AL), fibronectin (FN), and hyaluronic acid (HA) in 16 children aged 2-32 months without pulmonary inflammatory or parenchymal disease to establish reference values. We compared our data to those reported in older children and in normal adult volunteers. BAL results were obtained simultaneously from the right middle lobe and the lingula. Results indicated that children younger than 3 years of age had a higher number of cells/mL than older children and adults (59.9 x 10(4) vs. 17.6 x 10(4) and 12 x 10(4)). Differential cell count revealed that the percentages of alveolar macrophages (AM), lymphocytes (LYM), and eosinophils (EOS) were similar to those obtained in older children and in adults, whereas the percentage of neutrophils (NEU) was higher in younger children (NEU 5.5 vs 1.6 and 1.2%, respectively) than in older children and adults. The latter difference was even greater in infants under 12 months of age (NEU 7.6%). The concentrations of TP, AL, FN, and HA in children's BAL samples were compared to values reported for adults. There were no differences between infants and children 13-32 months of age or normal adults. BAL fluid obtained simultaneously from the middle lobe and lingula were not significantly different. In conclusion, this is the first report on BAL values (cellular and noncellular constituents) in children younger than 3 years. The results may be used as reference values for further studies in children with parenchymal lung disease in this age group.

Bronchoalveolar lavage studies in children without parenchymal lung disease: cellular constituents and protein levels

Bronchoalveolar lavage was performed on 12 healthy volunteers, comprising 6 smokers and 6 nonsmokers, of ages between 21 and 52 years The aim was to define normal variability of certain biochemical,

Bronchoalveolar lavage in the normal lung. First of three parts: protein, enzymatic and ionic features.

Bronchoalveolar lavage, performed on 15 healthy volunteers, enabled quantification and characterization of the alveolar cell populations. The subjects studied were 8 nonsmokers (5 males, 3 females) and 7 smokers (6 males, 1 female). It was found that in the smokers the macrophages increased compared with nonsmokers, both in absolute number (419,000 vs. 138,000/ml; p less than 0.005) and in percentage (93.8 +/- 3.0 vs. 88.1 +/- 4.8%; p less than 0.02), causing a significant increase in the total number of cells recovered after bronchoalveolar lavage (471,000 vs. 163,000/ml; p less than 0.005). Lymphocytes and neutrophils do not significantly vary in the two groups, even though among the smokers there is a tendency for the concentration of these cells to increase in the lavage liquids. The importance of the data obtained from healthy subjects lies in the possibility thus afforded of having reference values for the study of various lung pathologies with bronchoalveolar lavage.

M. Lusuardi

Papers

Bronchoalveolar lavage in the normal lung. First of three parts: protein, enzymatic and ionic features.

Bronchoalveolar lavage in the normal lung. 2. Cell distribution and cytomorphology.