Adherence to follow-up recommendations in asthma.

A cross-sectional study showed that 130 out of 1758 (8%) primary school children without a previous asthma diagnosis had undiagnosed asthma. Thirty-eight per cent of their parents refused to visit a general practitioner for this disorder. Factors associated with the refusal were high maternal education, mild symptoms and absence of airway reversibility.

Poor perception of dyspnoea in children with undiagnosed asthma.

The aim of the present study was to establish the differences in dyspnoea perception between children with undiagnosed and diagnosed asthma. A cross-sectional community-based study was performed, which included a parental questionnaire on the child's respiratory health and testing of airway reversibility and bronchial hyperresponsiveness (BHR). "Diagnosed asthma" was defined by a physician's diagnosis of asthma. "Undiagnosed asthma" was defined by the presence of asthma symptoms combined with either airway reversibility or BHR without a physician's diagnosis of asthma. Only children with a positive BHR test were selected for further analysis. Perception of dyspnoea was assessed using the Borg scale and the visual analogue scale (VAS), plotted against the percentage fall in forced expiratory volume in one second and expressed as the slope of the regression line. Of the initial 1,758 participating children, 70 had undiagnosed asthma and 38 had diagnosed asthma. The Borg and VAS slopes in children with undiagnosed asthma were less steep than those of children with diagnosed asthma (Borg: 0.07 and 0.14, respectively; VAS: 0.06 and 0.11, respectively). Among children with bronchial hyperresponsiveness, those without a parent's report of physician's diagnosis of asthma had a worse perception of dyspnoea than children with diagnosed asthma.

Diet and asthma in Dutch school children (ISAAC-2).

BACKGROUND: The rise in the prevalence of asthma in western societies may be related to changed dietary habits. Epidemiological studies in children have shown inverse associations of asthma related outcomes with intake of fruits, vegetables, dairy and whole grain products, and fish. In contrast to most previous studies, we used both questionnaire and clinical data to define asthma. METHODS: Intake of the abovementioned foods was studied in relation to asthma in 598 Dutch children aged 8-13 years. Dietary intake was estimated using a parent completed semi-quantitative food frequency questionnaire. Current wheeze and current asthma were defined based on questionnaire data. More complex end points were defined using information on bronchial hyperresponsiveness (BHR) and atopic sensitisation as well. Linear associations were studied using logistic regression analysis and odds ratios presented for the highest versus the lowest tertile of intake. In the final models, adjustments were made for maternal educational level, foreign descent, and total energy intake. RESULTS: The intake of whole grain products and of fish was inversely associated with asthma. Adjusted odds ratios for the independent associations with whole grains and fish were 0.46 (95% CI 0.19 to 1.10) and 0.34 (95% CI 0.13 to 0.85) for current asthma and 0.28 (95% CI 0.08 to 0.99) and 0.12 (95% CI 0.02 to 0.66) for atopic asthma with BHR. Similar results were observed for current wheeze and atopic wheeze with BHR. Intake of (citrus) fruits, vegetables, and dairy products showed no clear associations with asthma end points. CONCLUSIONS: Our findings suggest that a high intake of whole grain products and fish may have a protective effect against asthma in children.

Exhaled nitric oxide predicts airway hyper-responsiveness to hypertonic saline in children that wheeze.

BACKGROUND: Exhaled nitric oxide (eNO) has shown good validity for the assessment of airway inflammation in asthmatic children. In large-scale epidemiological studies, this method would be preferred above airway challenge tests, because it is a quick and easy applicable tool. OBJECTIVE: In this study, we aimed to assess the discriminatory capacity of eNO, and prechallenge FEV1 for airway hyper-responsiveness (AHR) in 8-13-year old schoolchildren. MATERIALS AND METHODS: Parents completed the ISAAC questionnaire, and children were tested for atopy, AHR to hypertonic (4.5%) saline (HS), and eNO. Diagnostic value was assessed by the area under the receiver operating curves (ROC), and calculation of positive and negative predicted values at different cut-off points for eNO and prechallenge FEV1. RESULTS: Areas under the ROC-curves of AHR were 0.65 for eNO and 0.62 for FEV1. Values increased to 0.71 and respectively 0.75 for a combined occurrence of AHR and current wheeze. Highest sensitivity and specificity were obtained at a cut-off value of 43 ppb for eNO and 103% predicted for FEV1. At these cut-off values, the positive predictive values for the presence of AHR in symptomatic children were respectively 83% (eNO) and 33% (FEV1), and negative predictive values in asymptomatic children were, respectively, 90 (eNO) and 80% (FEV1). CONCLUSION: Exhaled nitric oxide is a valid screening tool for AHR to HS in children that present with current wheeze, and it outperforms FEV1 as a predictor of AHR.

Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age.

BACKGROUND: There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions. OBJECTIVE: Examine independent effects on atopic sensitization and symptoms of day care attendance, older siblings, pet ownership, and early infancy's airway disease. METHODS: A cross-sectional survey among 8-13-year-old school children with complete data for 1555 children. RESULTS: After adjustment for confounders, atopic sensitization occurred less frequently in children that had attended a day care centre (OR: 0.73, 95% CI: 0.55-0.98) or had a cat or dog before 2 years of age (OR: 0.78, 95% CI: 0.61-0.99). Having older siblings yielded a nonsignificant trend towards protection (OR: 0.88, 95% CI: 0.70-1.11). For symptoms, there was no relation with having older sibs, day care attendance and pet ownership, although there was a trend towards protection for the combination of atopy and symptoms. In contrast, children with doctors' treated airway disease before age 2, more frequently reported recent symptoms of wheeze, asthma, rhinitis, or dermatitis (all P < 0.05). CONCLUSION: Early life environmental exposure to day care, or pets may protect against atopic sensitization. Protection against symptoms only occurred if atopic sensitization was present as well.

Airway responsiveness to hypertonic saline: dose-response slope or PD15?

The result of airway challenge test with hypertonic saline (HS) is expressed as the dose causing a 15% fall in forced expiratory volume in one second (FEV1; PD15). A noncensored measure, such as the dose-response slope (DRS), allows the evaluation of the risk of asthma for subjects with a fall in FEV1 <15%. The aim of this study was to assess the relationship between airway responsiveness to HS by PD15 or DRS, asthma symptoms and markers of eosinophilic inflammation. Data on current wheeze and airway responsiveness were obtained for 1,107 children (aged 8-13 yrs). Blood eosinophils and serum eosinophil cationic protein (ECP) were assessed in subsets (n = 683 and 485). PD15 was assessed if FEV1 fell > or =15%, and the DRS was calculated for all tests. Graphs were constructed to visualise relationships with current wheeze, blood eosinophils and serum ECP. Odds ratios and Spearman's correlation coefficients were calculated to quantify these relationships. Children with features of asthma had lower PD15 and higher DRS, and separation was most pronounced for DRS. Prevalence of current wheeze increased continuously over the entire range of DRS values. Blood eosinophils were significantly higher only for the highest values of DRS. In conclusion, the continuous relationship between airway responsiveness and asthma symptoms is in favour of a noncensored measure of airway responsiveness, such as the dose-response slope.

Bronchial hyper-responsiveness to hypertonic saline and blood eosinophilic markers in 8-13-year-old schoolchildren.

BACKGROUND: In adult asthma, bronchial hyper-responsiveness (BHR) to indirect stimuli reflects eosinophilic activation more closely than BHR to stimuli that directly cause smooth muscle contraction. AIM: To assess the relationship between BHR to the indirect stimulus hypertonic saline (HS), blood eosinophil numbers, and serum eosinophilic cationic protein (ECP) in children with and without current wheeze. METHODS: A cross-sectional survey among 8-13-year-old schoolchildren, using the International Study of Asthma and Allergic disease in Childhood questionnaire, bronchial challenge with HS, skin prick tests, serum IgE, blood eosinophil counts and ECP (in a subset). Based upon the presence of current wheeze (WHE) and BHR, we defined three case groups (WHE+BHR+, WHE-BHR+, WHE+BHR-) and the reference group (WHE-BHR-). By regression analyses, each case group was compared with the reference group for differences in atopic sensitization, blood eosinophil counts and serum ECP. RESULTS: Complete data were obtained for 470 children. BHR was present in 103 children (22%), 66 being asymptomatic and 37 symptomatic. Children of all three case groups were more often atopic. Sensitization to indoor allergens particularly occurred in children with BHR, irrespective of symptoms (P < 0.05). Children with WHE+BHR+ had highest values for blood eosinophils and serum ECP (P < 0.05). Children with WHE-BHR+ had less severe responsiveness. In atopic children with WHE-BHR+, serum ECP was higher than in children with WHE-BHR-(P < 0.05). CONCLUSIONS: BHR to HS is associated with blood markers of eosinophilic activation, particularly in atopic children.

Immunoglobulin G4 antibodies to rat urinary allergens, sensitization and symptomatic allergy in laboratory animal workers.

BACKGROUND AND OBJECTIVES: We have previously reported that high rat urinary allergen (RUA) exposure was not associated with increased risk of rat allergy in long-term-exposed laboratory animal (LA) workers. We aimed to assess whether strong allergen-specific IgG4 responses could explain the absence of a dose response in these subjects. We investigated whether IgG4 was associated with allergen exposure and prevalence of sensitization or respiratory symptoms to rats. The longitudinal relation between IgG4 and rat allergy was studied using data obtained during 2 years of follow-up. METHODS: Five hundred and twenty-nine LA workers answered a questionnaire on respiratory symptoms and occupational history and participated in skin prick testing. Blood samples were analysed for specific IgG4 and IgE to RUA. Exposure to RUA was estimated based on personal air samples. The relation between IgG4 and newly occurring sensitization or rat allergy was studied in workers who were not sensitized or did not report respiratory symptoms to rats. RESULTS: IgG4 titres were higher in atopic than in non-atopic subjects, and increased with higher allergen exposure. Titres were highest in subjects who were sensitized and reported respiratory symptoms to rats when compared with those who were not (geometric mean [geometric standard deviation] = 202 [5.7] vs. 8.4 [18.3] AU). The association between IgG4 and sensitization or symptomatic rat allergy was independent of estimated allergen exposure. IgG4 was a strong predictor of newly occurring sensitization and symptomatic rat allergy during follow-up in atopic and rat-sensitized subjects. CONCLUSION: High exposure to RUA is associated with a strong allergen-specific IgG4 antibody response. High anti-RUA IgG4 is a strong predictor of prevalent and incident sensitization and symptomatic rat allergy in atopic and rat-sensitized subjects. IgG4 can therefore not explain the absence of a dose response between allergen exposure and allergy in long-term-exposed workers. We consider anti-RUA IgG4 to be a marker that combines aspects of exposure and susceptibility.

Lung function decline in laboratory animal workers: the role of sensitisation and exposure.

BACKGROUND: Little is known about the relation between allergic sensitisation and subsequent long term lung function changes in working populations exposed to sensitising agents. AIMS: To investigate whether exposure and work related sensitisation to laboratory animals are associated with lung function decline. METHODS: The relation between exposure and sensitisation to laboratory animal allergens and changes in lung function was investigated in a longitudinal study (median follow up 2.0 years) among 319 laboratory animal workers. Subjects who had been working with laboratory animals for less than 4 years (n = 102) were analysed separately, since an earlier cross sectional analysis had suggested a strong healthy worker effect in more experienced workers. RESULTS: In multiple regression analyses both sensitisation and exposure appeared to contribute independently to lung function decline in subjects who had been working with laboratory animals for less than 4 years, adjusting for gender, age, smoking, and atopy. Lung function decline was most pronounced in sensitised subjects who continued to be in contact with the animals to which they were sensitised, with estimated average excess declines in FEV1, FVC, and MMEF of 83 ml/y (p < 0.05), 148 ml/y (p < 0.01), and 7 ml/s/y (p = 0.9). CONCLUSIONS: We conclude that exposure to laboratory animals is a significant risk factor for accelerated lung function decline, and that sensitised workers are especially at risk.

Bronchial responsiveness to adenosine-5'-monophosphate and methacholine as predictors for nasal symptoms due to newly introduced allergens. A follow-up study among laboratory animal workers and bakery apprentices.

BACKGROUND: In asthma patients, bronchial hyper-responsiveness (BHR) to adenosine-5'-monophosphate (AMP) reflects bronchial inflammation more closely than BHR to methacholine. In this follow-up study we studied bronchial responsiveness to both stimuli as predictors of new-onset airway symptoms. METHODS: We included 118 laboratory animal workers and bakery apprentices with a work experience of maximally 1 year. The baseline survey comprised a questionnaire, skin prick tests (SPTs) to common and work allergens, blood eosinophil counting, and bronchial challenge with methacholine and AMP. At follow-up, questionnaire and SPTs to work allergens were repeated. Airway symptoms to common allergens and work allergens were defined as nasal symptoms, chest tightness or asthma attack during or after contact with either common or work allergen. Bronchial challenge tests were analysed by BHR at a 15% fall in forced expiratory volume of 1 s (FEV1), and by dose-response-slope (DRS). RESULTS: Fourteen subjects (12%) developed airway symptoms to work allergens, of whom 12 had nasal symptoms. A positive SPT to work allergens occurred in 64%, and was the strongest predictor of airway symptoms [relative risk (RR) 7.5, 95% confidence interval (CI) 2.0-28.6]. Other predictors were airway symptoms to common allergens (RR 4.3, 95% CI 1.4-12.8), blood hypereosinophilia (RR 4.4, 95% CI 1.2-15.4) and BHR, with a slightly higher risk estimate for AMP than for methacholine (RRAMP 3.7, 95% CI 1.1-12.5 and RRmeth 2.8, 95% CI 1.0-8.5). The difference was more distinct analysing airway responsiveness by DRS, for which AMP predicted symptoms better than methacholine (P < 0.05). CONCLUSIONS: Pre-existent bronchial inflammation or a preinflammatory state marked by AMP (hyper)responsiveness increases the vulnerability to develop nasal symptoms.

Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children.

BACKGROUND: Exhaled nitric oxide (eNO) may serve as a non-invasive marker of airway inflammation but its relationship with other commonly used measures has not been evaluated. METHODS: Levels of eNO in a sample of 450 children aged 7-12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV(1) and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. RESULTS: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV(1) and MMEF were not associated with eNO levels. CONCLUSIONS: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.

The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children.

BACKGROUND: Exhaled nitric oxide (NO) has been proposed as novel a non-invasive marker of airway inflammation. OBJECTIVE: The level of exhaled NO was determined in a random sample of school children (7-12 years old) with the aim of investigating the relationship between exhaled NO and sensitization to common allergens. RESULTS: In the 450 children tested by skin prick tests (SPT), the prevalence of sensitization was 29.5% (overall), 21.9% (sensitization to indoor allergens), and 15.0% (sensitization to outdoor allergens). Regression analysis showed that levels of exhaled nitric oxide were closely associated with various measures of sensitization to aeroallergens. Sensitization to indoor allergens was associated with higher levels of exhaled NO (eNO) than sensitization to outdoor allergens when assessed by IgE but not when assessed by SPT. Children with reported wheeze in the past 12 months had much stronger associations between sensitization and eNO than children without wheeze. CONCLUSION: We conclude that allergic sensitization is strongly associated with increased levels of exhaled NO, especially in children with wheeze.

Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children.

BACKGROUND: Studies have suggested that early contact with pets may prevent the development of allergy and asthma. OBJECTIVE: To study the association between early, current and past pet ownership and sensitization, bronchial responsiveness and allergic symptoms in school children. METHODS: A population of almost 3000 primary school children was investigated using protocols of the International Study on Asthma and Allergies in Childhood (ISAAC). Allergic symptoms were measured using the parent-completed ISAAC questionnaire. Sensitization to common allergens was measured using skin prick tests (SPT)s and/or serum immunoglobulin (Ig)E determinations. Bronchial responsiveness was tested using a hypertonic saline challenge. Pet ownership was investigated by questionnaire. Current, past and early exposure to pets was documented separately for cats, dogs, rodents and birds. The data on current, past and early pet exposure were then related to allergic symptoms, sensitization and bronchial responsiveness. RESULTS: Among children currently exposed to pets, there was significantly less sensitization to cat (odds ratio (OR) = 0.69) and dog (OR = 0.63) allergens, indoor allergens in general (OR = 0.64), and outdoor allergens (OR = 0.60) compared to children who never had pets in the home. There was also less hayfever (OR = 0.66) and rhinitis (OR = 0.76). In contrast, wheeze, asthma and bronchial responsiveness were not associated with current pet ownership. Odds ratios associated with past pet ownership were generally above unity, and significant for asthma in the adjusted analysis (OR = 1.85), suggesting selective avoidance in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only showed an inverse association with sensitization to pollen: OR = 0.71 for having had furry or feathery pets in general in the first two years of life, and OR = 0.73 for having had cats and/or dogs in the first two years of life, compared to not having had pets in the first two years of life. CONCLUSION: These results suggest that the inverse association between current pet ownership and sensitization and hayfever symptoms was partly due to the removal of pets in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only seemed to offer some protection against sensitization to pollen.

Repeatability of bronchial hyperresponsiveness to adenosine-5'-monophosphate (AMP) by a short dosimeter protocol.

BACKGROUND: To study bronchial responsiveness to adenosine 5'-monophosphate (AMP) in population surveys, repeatability of a rapid dosimetric method with quadrupling doses was evaluated. METHODS: Volunteers with symptoms of airway respiratory allergy or asthma were invited for AMP challenges on two occasions. After each dose the fall in forced expiratory volume in one second (FEV(1)) compared with the post-saline value was determined. The cumulative doses of AMP needed to cause a fall in FEV(1) of 20% (PD(20)), 15% (PD(15)), and 10% (PD(10)) were calculated. Agreement was evaluated by means of kappa values. After excluding systematic differences in PD values on two occasions (t test), repeatability of a single estimation of the chosen PD values was calculated and expressed in doubling doses (DD). RESULTS: In 28 of 76 subjects a PD(20) was estimated on the two visits, in 29 subjects a PD(15) was estimated, and in 32 a PD(10) was obtained. Kappa values for a positive threshold were 0.89 for a cut off level for a 20% fall in FEV(1), 0.78 for a 15% fall in FEV(1), and 0.76 for a fall in FEV(1) of 10%. The PD values did not differ between the two visits and 95% repeatability of a single estimation was +/-1.7 DD for PD(20), +/-2.2 DD for PD(15), and +/-2.4 DD for PD(10). The quadrupling dose method reduced time by 40% in non-hyperresponsive subjects and no adverse effects were observed. CONCLUSION: The short dosimeter protocol with quadrupling doses for AMP challenges is a rapid, reproducible tool for estimating bronchial responsiveness in population surveys.

Infant respiratory symptoms in relation to mite allergen exposure.

The relationship between the Dermatophagoides pteronyssinus (Der p) I content of house dust and the respiratory symptoms reported for young infants was studied. One hundred and four infants, aged 3-15 months, were selected during July-September 1993 through the Dutch postnatal health care service, using a short screening questionnaire to identify mothers with respiratory allergy to house dust and/or pets. Forty-eight were selected from this group of mothers ("high risk" infants) and 56 infants were selected when neither of the parents reported allergy or chronic respiratory symptoms ("low risk" infants). All homes were visited in October 1993. Dust samples were collected from the infant's mattress and from other places in the home, and the Der p I content was measured in dust extracts. The results indicate that on more than half of the mattresses, the Der p I level was over 2,000 ng.g-1, the level suggested to be associated with an increased risk of sensitization. Information on respiratory symptoms ("wheeze" and "prolonged cough") experienced since birth was obtained by questionnaire from one of the parents on the dust sampling day. The occurrence of respiratory symptoms in the infants appeared to be positively related to the Der p I concentration of the dust. Although no objective measurements of respiratory symptoms were available, the results of this study suggest that exposure to mite allergen in early life may lead to respiratory symptoms that are suggestive of airway obstruction in the first year of life.

Der p I concentrations in mattress surface and floor dust collected from infants' bedrooms.

BACKGROUND: Allergen exposure in early childhood is thought to be important for sensitization and subsequent development of asthma. Not much is known, however, about exposure of young children to allergens in the home. OBJECTIVES: This study was designed to document dust mite allergen exposure in young children, and to determine whether infants from atopic mothers (= 'high-risk' infants) are exposed to lower concentrations of house dust mite allergen than infants from non-atopic parents (= 'low-risk' infants). METHODS: Dust samples were taken in the homes of 104 infants (48 'high-risk' and 56 'low-risk' infants, selected by questionnaire) aged 3-15 months, from floors in different rooms and from the child's mattress surface. RESULTS: The majority of the infants were found to be exposed to Der p I concentrations of more than 2000 ng/g in dust collected from the surface of their mattresses. Lower Der p I concentrations were found in mattress surface dust from the beds of infants from atopic mothers than of infants from non-atopic parents. Also, lower Der p I concentrations were found in floor dust from the homes of infants from atopic mothers. Infant beds equipped with new mattresses, new blankets and top plastic sheeting had significantly lower Der p I concentrations than beds equipped with used mattresses and blankets, without top plastic sheeting. CONCLUSIONS: Young children in the Netherlands are exposed to significant concentrations of Der p I in mattress surface dust. Allergic parents appear to provide their children with environments somewhat less rich in mite allergen than non-allergic parents.

Associations of PM10 and airborne iron with respiratory health of adults living near a steel factory.

The association between daily PM10 (particles with a median aerodynamic diameter of < or = 10 microns) and iron particle concentrations and respiratory health was studied in a population of adults selected for current or recent bronchodilator use. Acute changes in respiratory health were measured as changes in peak expiratory flow (PEF), and daily prevalence of respiratory symptoms and medication use as recorded in a diary. The study period was October 11 through December 22, 1993. The study population included 32 adults living near a large steel industry in Wijk aan Zee, the Netherlands. During the study period, 24-h average PM10 concentrations in Wijk aan Zee ranged from 36 to 137 micrograms/m3 while the 24-h average concentrations of iron, silicon, sodium, and manganese ranged from approximately zero to 6.95, 1.84, 12.02, and 0.37 micrograms/m3 respectively. The steel industry was found to contribute significantly to the PM10 concentrations, and especially to the iron and manganese concentrations in the air. The association of changes in respiratory health with changes in PM10, iron, sodium, and silicon was evaluated using a time series approach. A statistically significant decrease in PEF was found to be associated with increasing PM10 concentrations. Stronger associations were found for smokers than for nonsmokers, and for subjects reporting many chronic respiratory symptoms than for subjects reporting few such symptoms. Increased concentrations of iron tended to be associated with a decline in PEF, with a lag of 2 to 3 d, although the association did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Rising case fatality of bacteriologically proven pulmonary tuberculosis in The Netherlands.

Analysis of registration cards from the Tuberculosis Control Program (TCP) showed a four-fold increase in case fatality of bacteriologically proven pulmonary tuberculosis in Dutch patients in the period 1973-1984. Registered data of 125 deceased patients whose primary cause of death was pulmonary tuberculosis were analyzed. Increased case fatality predominantly occurred in the elderly. Elderly patients presented often with other, less specific, complaints than coughing, but had a shorter combined patient's and doctor's delay than younger patients. The elderly were more often treated with 3 tuberculostatic drugs (INH, pyrazinamide, rifampin). Bacterial resistance was found in only 2%. Probably the most important factor concerning the raised case fatality in the elderly is the decline in immune response, due to ageing of the Dutch population. An effective response to tuberculostatic drugs needs a reasonably intact immune response. Declining immunity of the elderly group will increase incidence and mortality of pulmonary tuberculosis in this group.