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Epidemiological and clinical data are discussed dealing with a possible influence of inflammatory changes of the nasal and especially the paranasal tissue on lower airway disease like asthma, the so-called "sinobronchial syndrome". Even though there is clear evidence of an association of the upper with the lower airway diseases, a causal relationship and a possible work of action are still up for discussion. The literature has been reviewed, and different theories are discussed. Generally speaking, a branch of differently accentuated mechanisms seems to play a role.

According to national and international recommendations the bronchial sensitivity should be determined based on the decrease of the FEV1 by 20 % (FEV1 - 20) or the increase of the airway resistance by means of body plethysmography by 100 % (Raw + 100). Measurement of airway resistance by interrupter technique (Rint) is a simple method and needs no active cooperation of the patient, but is not recommended in airway challenge testing. We investigated the role of the increase of Rint by 100 % (Rint + 100) compared to Raw + 100 and FEV1 - 20 during carbachol airway challenge testing by means of dosimetry. We examined 123 patients with following symptoms: 85 x coughing, 31 x coughing and dyspnea, 7 x medical opinion. Significant correlations between Rint and Raw were found before and after the challenge tests (Rint before/after 0,3 +/- 0,13/0,36 +/- 0,25 kPa*s/l; Raw before/after 0,24 +/- 0,09/0,50 +/- 0,41 kPa*s/l; r = 0,504/0,672; p < 0,001 [Pearson]). The median values of Rint and Raw were significantly different (p < 0,001 [Wilcoxon]). Moreover Rint systematically overestimated airway resistance in the normal range and underestimated the increase of airway resistance during challenge testing (r = 0,783; p < 0,001 [Pearson]). In 58 patients an increased airway responsiveness was found. In 21 oft these patients there was no increase of Rint above the initial value. Sensitivity/specificity/positive predictive value/negative predictive value in % to the detection of airway hyperresponsiveness were in Rint + 100 9/95/63/54, in FEV1 - 20 61/100/100/66 and in Raw + 100 98/100/100/98. In conclusion we found significant correlations between Rint and Raw, but the median values were systematically and significantly different. Rint + 100 had a low sensitivity to detect airway hyperresponsiveness and is not comparable with FEV1 - 20 or Raw + 100.

Airways of patients with bronchial hyperreactivity (BHR) are characterised by exaggerated bronchoconstriction in response to a variety of stimuli; bronchospasm may be elicited during induction and maintenance of anaesthesia. The prevalence of BHR in normal populations is approximately 10%. BHR is an important feature of clinical asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis, atopy, upper respiratory tract infections and smoking. This review will outline some important aspects of the pathophysiological basis of BHR, i.e., neural and inflammatory mechanisms. Furthermore, it should assist in identifying patients at risk and update perioperative anaesthetic considerations. Prophylaxis of airway reflex activation and an appropriate anaesthetic plan should prevent airway constriction. Since tracheal intubation is the major risk factor to induce bronchospasm intubation should be avoided whenever possible and regional anaesthesia preferred. If tracheal intubation is unavoidable, propofol and ketamine can be recommended as induction agents. Prophylaxis of intraoperative bronchospasm and initial therapy, such as deepening of anaesthesia, inhalational administration of sympathomimetics and anticholinergics, and i.v. use of local anaesthetics and corticosteroids are outlined. Despite its popularity theophylline offers little benefit during anaesthesia. Adequate preoperative evaluation and preparation of the patient with BHR will contribute to optimising anaesthetic management of patients with BHR.

Our own investigations comprising 23,174 patients suffering from sleep apnoea showed that about 4 per cent of these patients suffer from a hyperreactive bronchial system. In some of these patients treatment with nCPAP causes coughing or mild dyspnoea even after having been previously asymptomatic. Loss of water and heat on the surface of bronchial mucosa may induce reversible bronchoconstriction. We examined in 60 patients suffering from obstructive sleep apnoea whether mechanical treatment with nCPAP would cause a change in bronchial reactivity. Cold air hyperventilation was used in provocation testing. Provocation tests were performed before and after a 3-day treatment with nCPAP in the early morning. In some patients with previously positive reaction, application of nCPAP alone decreased the lung function. Cold air hyperventilation challenge may be helpful to detect possible risks in patients using nCPAP, and to minimise such risks.

In patients with obstructive sleep apnoea (OSA) nCPAP may irritate the mucous membranes of the upper airways. We investigated in this study whether nCPAP can induce bronchial hyperreactivity (BHR). Forty-one patients (33 men, mean age 52.6 years) were treated with nCPAP due to OSA. All of them were tested for BHR with histamine ("pari-provo-Test") before and six weeks after initiation of the nCPAP therapy. Thirty-five of the patients showed BHR neither before nor after the beginning of CPAP. Six patients developed a BHR of moderate degree (PD20: 50-100 micrograms) during the study; four of these six patients were not symptomatic. The two other patients complained about more colds than usual or about noctumal cough. Both of them received inhaled steroids and a moistening system. Nobody of the enrolled patients was obliged to finish CPAP therapy due to BHR. Four patients had already a BHR before nCPAP therapy began. Most of the patients did not acquire a BHR during the first 6 weeks after nCPAP therapy had started. A BHR bronchial may develop, but in the majority it remains without clinical relevance. In patients with a BHR and OSA, the benefits of nCPAP therapy excel the potential adverse effects.

Own results of 23,174 patients suffering from sleep apnoea syndrome showed that about 4 per cent of these patients have an increase of bronchial reactivity. In 60 patients with assured bronchial hyperreactivity we performed an inhalative bronchial provocation test using carbachol. Tests were performed before and after two days of treatment with nCPAP in the early morning. 23 of our 60 patients showed a decrease of PD20 FEV1 after nCPAP. The other patients did not show any significant differences. Our results demonstrate that in patients with increased bronchial reactivity, nCPAP therapy may aggravate bronchial hyperreactivity.

Nocturnal asthma-especially night cough are sometimes the first and only symptom of the beginning disease in childhood and are then often misinterpreted. The cause of nocturnal asthma seems to be a circadian rhythm of hormones and mediators, much more predominant in asthmatic than in healthy children. Moreover, there are some evidences, that also other factors--i.e. inflammation, number of T-helper cells and beta-receptors, allergen contact a.o.--influence this process leading to a deterioration of bronchial reactivity and lung function. Furthermore children with stable asthma show a prolonged expiration time during sleep compared to healthy children. Nocturnal asthma calls for an intensification of therapy. Besides the removal of allergen sources (HDM) and a warranty of free upper airways (adenoids), drug therapy should be optimised. This applies for the basic antiinflammatory treatment as well as for the use of long acting bronchodilators. The relatively high demand for beta-agonists in children and the age dependence of half-life for theophylline must be considered.

Control of breathing, bronchomotor tone and lung function are inferior to circadian rhythms, which can already be demonstrated at healthy subjects. They get relevant especially at patients with obstructive airway disease and sleep disturbances. Particularly in the early morning hours flow resistance in the airways and in the nose rises. Several different mechanisms are suspected to be responsible: Allergen exposure in bed, supine position, interruption of the bronchodilator therapy, gastro-oesophageal reflux, tenseness of the airways and secretory accumulation. Connected to nocturnal asthma might also be an increased airway responsiveness. Several factors contribute to nocturnal asthma, but they don't constitute a general concept for the explanation of nightly exacerbations. Many hormonal neural cellular and humoral factors show diurnal fluctuations which favour a constrictive bronchial response in the night. Diurnal or ultradian changes in O2 and CO2 sensitivity only play a minor role. However, we have to realise alterations in the responses of the central neuronal control mechanisms of breathing within the respiratory cycle. Oscillations of arterial CO2 partial pressure or pH-values influence tidal volume and ventilation directly. Circadian changes of different vital functions cause minor alterations in airway responsiveness and airway resistance in normal subjects, however in patients with asthma they are enlarged in amplitude and become relevant especially in the night and early morning hours.

Within the framework of unspecific inhalation provocation tests with pharmacological substances for the purpose of diagnosing bronchial hyperreactivity, the cholinergics methacholine and carbachol are often used besides histamine. We examined 21 patients with known bronchial hyperreactivity in the symptom-free interval using the methacholine inhalation provocation test and 15 hyperreactive patients using the carbachol inhalation provocation test with the purpose of determining the extent to which methacholine and carbachol differ from each other in respect of their effect. Standard reference values were the provocation doses PD100/0.5Rt and PD20FEV1. It was found that methacholine and carbachol exercise an equivalent effect in the inhalation provocation test. No statistically significant difference for the provocation doses PD100/0.5Rt and PD20FEB1 was seen in group comparisons.

Of the 8,973 patients with sleep related breathing disorders examined in our department, about 4% were found to have a hyperreagible bronchial system. Provocation tests were performed before and after a 3-day CPAP therapy in 8 male patients with confirmed bronchial hyperreagibility. Two of these 8 patients revealed a marked increase of the respiratory path resistance and a decrease in FEV1.0 of 30% in the provocation test after 3 days. This did not occur with the other patients. From these findings, it is concluded that CPAP therapy can lead to an increase in the hyperreagibility in some patients with hyperreagible bronchial systems. However, further investigations are needed to identify the underlying causal relationships.

Bronchial asthma is a chronic inflammatory disease of the airways which triggers bronchial hyperresponsiveness and reversible airflow obstruction. Today it is still a potentially fatal disease. The course and prognosis of bronchial asthma can be improved by adequate diagnosis, education of patients to develop a partnership in disease management, continuous monitoring of asthma severity, avoidance of asthma triggers, establishment of medication plans for chronic management as well as for managing exacerbation, and regular follow-up care. In the following 5 case reports each of these factors is discussed in detail.

There are significant bioperiodicities for hormonal, neural, cellular, and humoral factors as well as for mediators. A combination of these findings is an explanation for the increased hyperreactivity in patients with allergic diseases during the night. In the morning hours between 2 and 6 a.m., the histamine concentration shows a peak, adrenaline and cyclic AMP have their minimum, while cortisol secretion is just ascending. Circadian variations are also seen with respect to the density of beta-receptors. Thromboxane A2 shows a peak during the night, PGE2 is depressed, a finding also in favour of bronchial constriction. Total plasma protein IgA, IgM, IgG and IgE show a distinct bioperiodicity with a minimum during the night, cellular elements like T11, T4 and B-lymphocytes, and Leu8 have a maximum. The nocturnal symptom exacerbation must be given the fullest attention in choosing the time of administration of the appropriate medication.

Background: Nonspecific bronchial hyperreactivity (BHR) is under discussion as a possible risk factor for the development of chronic obstructive pulmonary disease., Method: Within the framework of a prospective study, we investigated the course of the disease in 50 inpatients with BHR, and the clinical symptoms of airways disease (coughing, dyspnea and expectoration) with no manifest airways obstruction at rest (Rt < 3.5 cm H2O/l/s) on admission to the hospital. The unspecific inhalative provocation challenge was carried out with metacholine. The presence of BHR was assumed when the resting respiratory resistance (Rt) of < 3.5 cm H2O/l/s increased to more than 6 cm H2O/l/s. On admission to hospital, all the patients were treated with inhalative bronchodilators and glucocorticosteroids., Results: After an average period of 2.8 years, BHR was no longer measurable in only 7 of the patients (14%), while 28 patients (56%) continued to have a BHR with clinical symptomatology presenting. In 15 patients (30%), manifest airways obstruction at rest, with an average Rt of 6.4 cm H2O/l/s developed. In patients with an uncharacteristic cough, dyspnea and unremarkable lung function parameters at rest, a provocation test should be done to identify BHR. A prognosis can, however, not be established on the basis of a single demonstration of BHR, but only after observation over a longer period.

Until recently asthma was considered to be caused mainly by bronchospasm of the smooth airway musculature. Accordingly beta-adrenergic agonists were the drugs of choice. During the last decade, however it has become increasingly clear that ongoing chronic inflammation of the bronchial wall plays a prominent role in the disease process. During the early bronchoconstriction after allergen challenge, histamine is probably the most important mediator. The late reaction is characterized by an inflammatory infiltration of the bronchial wall, notably by eosinophils and lymphocytes. A complex interplay of mediators as leukotrienes, prostaglandins and PAF may lead to a chronic inflammation. Inflammatory changes are seen in bronchial biopsies and broncho-alveolar lavage fluid even of mild and asymptomatic asthmatic patients. Based on this new disease concept, antiinflammatory drugs have become the mainstay of therapy even in mild to moderate asthmatics. Beta-adrenergic agonists remain the most important drug for the relief of acute bronchospasm.

Physical exercise can induce an acute attack in most asthmatics. Exercise-induced asthma (EIA) is therefore a common clinical presentation of bronchial asthma. EIA is likely a consequence of bronchial hyperreactivity whereby alterations in bronchial osmolarity, heat-loss by hyperventilation and physical activity per se are discussed as pathogenic triggers. Clinical presentation, pathogenesis and diagnosis of exercise-induced asthma are summarized. Pharmacologic and non-pharmacologic possibilities are covered in some depth. In this context the value of sports-therapy in treatment of asthma is redefined. The possibilities and limitations for this form of treatment are explained.

Bronchial hyperreactivity (BHR) can be proved by various methods. 21 children, 14 asthmatics and 7 healthy subjects were submitted to inhalative methacholine challenge as well as to 'free running' as a form of exercise challenge in a randomized sequence. For the methacholine inhalation a standardized procedure was followed and the provocative concentration defined (PC20) at which a decrease of more than 20% in FEV1 was found. There is no real standardisation for 'free running' (concerning temperature and humidity of the inspired air; individual level of exercise) but subjects had to run for 6 minutes while the heart rate should have been between 170 and 180 beats/minute. This increase in pulse rate relates to a submaximal work at which 60-85% of maximal O2 uptake are obtained. A decrease of 15% from basic value of FEV1 was defined as a positive result. By the use of methacholine inhalations we found 16 children (14 diseased, 2 controls) to be hyperreactive, whereas only 3 of them showed a positive result after 'free running'. We conclude, that firstly, methacholine provocations and exercise challenges assess different kinds of bronchial reactivity, secondly, 'free running' as a form of exercise is very difficult to standardize and therefore prone to errors and thirdly, 'free running' is not sensitive enough to assess BHR in children with mild asthma bronchiale if used as the only form of challenge. Problems concerning measurement of BHR are discussed.

For measuring the interoception of airway resistance, bronchial obstructions are often simulated by flow-resistive loads applied externally (i.e. outside the body) into the respiratory flow. However, it is open to doubt whether interoception characteristics obtained in this manner are really related to the clinical pattern of complaints of asthmatic patients. Possibly such externally applied resistance simulates merely an aspect of the physics of apnoea but not a clinical and hence also psychological aspect of the same. To estimate the significance of these aspects for the perception of obstructions, this ability was measured in 25 asthmatic patients first by means of external added loads; this test was then repeated by noting the subjective assessment of bronchial obstructions caused during a routine histamine provocation test. Both interoception parameters correlated only slightly (rxy = 0.31) which is discussed as a pointer to the assumption that, among other parameters, psychological factors may considerably modify the perception of flow resistivity. No correlations were seen between the characteristic interoception value obtained by means of mesh resistivities and the different variables of the clinical pattern of symptoms. On the other hand, the interoception parameter measured on the basis of bronchial obstructions revealed significant connections with several clinical variables: the greatly increased incidence of respiratory distress at night or during certain external conditions, coping medication, physical exercise and style. It is concluded that only such parameters of perception of obstructions are clinically relevant for patients suffering from asthma, which consider not only the somaticophysical but also the psychic component of asthmatic respiratory distress.

A case of a 10-year old boy suffering from asthma bronchiale following pleuropneumonia is reported. Paradoxically, bronchospasmolysis tests using physiological saline + salbutamol or ipratropium bromide impaired the lung function of this patient. Salt solutions inhaled in increasing doses until 1.4% generated severe bronchoconstriction, however, inhalation of DNCG + salbutamol normalized the lung function completely.

The bronchial hyperreactivity alone does not stand for illness but it is typical of asthma. Nonspecific tests are on a low level of standardization and the results of various research groups are difficult to compare. We used the free running provocation test compared with the inhalation test of acetylcholine in a routine lung function laboratory. Using the flow-volume curve both methods were of a comparable value although not absolute equal. Running-provocation seems to be especially qualified for the ascertainment of exercise-induced bronchospasm. A preexisting obstruction more often led to a positive result with increased reaction. The MEF values on low level of FVC proved to be especially sensitive. Free-running using the flow-volume curve for evaluation of ventilation is a cheap, noninvasive, natural, and in our opinion qualified method for the estimation of nonspecific bronchial hyperreactivity.

To study the physiological response to cold air challenge, the "flow-volume-loop" method was used. Fifty-one healthies (31 males and 20 females, mean age 30 +/- 9 years) served as the subjects. Measurements were done before and subsequently 5 and 30 min after challenge. In normal subjects it were observed both an increase and decrease of the airway obstruction. All registered changes were statistically significant. The range of normal alterations of parameters as a response to the cold air challenge was calculated on the base of obtained data.