European Respiratory Journal

The platelet has traditionally been associated with disorders of the cardiovascular system; a well-recognized cell type actively involved in the maintenance of haemostasis and the initiation of repair following tissue injury. It has been accepted that the primary function of platelets is their adhesion to the endothelium or to other components at sites of the injured vessel wall in the initiation of haemostasis. However, it has been suggested that the fundamental physiological role of the platelet within the mammalian circulation is in the defence of the host against invasion by foreign organisms. Studies from several groups suggest an important role of the platelet in allergic processes and immunological mechanisms. In this review, we have summarized the origin, physiology, activation and function of the platelet, in addition to both experimental and clinical evidence implicating the involvement of this cell type in certain human lung diseases.

Gefitinib is a potent drug used in the treatment of nonsmall-cell lung cancer (NSCLC).

Gefitinib acts by inhibition of the epidermal growth factor receptor tyrosine kinase. Clinical trials have confirmed the efficacy of gefitinib for NSCLC. Adverse drug reactions, although frequent, are mild, and include acne-like skin rash and diarrhoea.

The present study describes the case of a 56-yr-old male with NSCLC who, 4 weeks after treatment with gefitinib, suffered from a severe alveolar haemorrhage diagnosed by bronchoalveolar lavage.

This is the first case report of an acute life-threatening lung injury in a patient with nonsmall-cell lung cancer who had been given gefitinib.

Airborne particles are associated with adverse health effects and contribute to excess mortality in epidemiological studies. A recent hypothesis proposes that the high numbers of ultrafine (<0.1 μm diameter) particles in ambient air might provoke alveolar inflammation and subsequently cause exacerbations in pre-existing cardiopulmonary diseases.

To test the hypothesis adult asthmatics were followed with daily peak expiratory flow (PEF) measurements and symptom and medication diaries for six months, while simultaneously monitoring particulate pollution in ambient air. The associations between daily health endpoints of 57 asthmatics and indicators of air pollution were examined by multivariate regression models.

Daily mean number concentration of particles, but not particle mass (PM₁₀(particle mass <10 μm), PM_2.5–10, PM_2.5, PM₁), was negatively associated with daily PEF deviations. The strongest effects were seen for particles in the ultrafine range. However, the effect of ultrafine particles could not definitely be separated from other traffic generated pollutants, namely nitric oxide, nitrogen dioxide and carbon monoxide. No associations were observed with respiratory symptoms or medication use.

Particle mass measurements can be strongly influenced by mechanically produced, soil-derived particles, which may not be associated with adverse health effects. Therefore, air quality monitoring should include particle number concentrations, which mainly reflect ultrafine particles.

A 43 year old woman presented with two large bilateral tumours of the first ribs that compressed the right subclavian vessels, trachea and oesophagus and led to right arm oedema, severe dyspnoea and dysphagia. The resected tumours showed typical histological features of fibrous dysplasia without malignant transformation. The right tumour weighed 1.5 kg and measured 17 x 13 x 10 cm. This report demonstrates that major surgery is still possible for resection of such exceptional giant compressive lesions, since fibrous dysplasia is a benign and non-infiltrative tumour.

It has been reported that quantitative computed tomography (CT) scanning of the lungs showed decreased progression of emphysema in a randomised clinical trial in patients with severe α₁‐antitrypsin (α₁‐AT) deficiency receiving monthly intravenous augmentation therapy with human α₁‐AT. Comparable results were not obtained using rate of decline of forced expiratory volume in one second.

Accordingly, the Alpha‐1 Foundation convened a workshop to explore the feasibility of using quantitative CT data as a primary outcome variable in trials of drugs for treating α₁‐AT deficiency.

This report reviews the following: the principles for the use of modern CT scanners for quantifying emphysema; the methods and data on validation by comparison with measurements of severity of emphysema in inflation-fixed specimens of lungs; and the possibility of decreasing radiation dosage from CT to make it safe and ethically possible to use CT in longitudinal studies.

The workshop concluded that it is feasible, safe and ethically possible to use computed tomography in longitudinal studies of emphysema. It recommended that the primary end-point should be a significant shift in the 15th percentile of lung density.

We investigated the relationship between airway calibre and the dose and distribution of inhaled aerosol in ten normal and six asthmatic subjects. Subjects inhaled saline aerosol containing 99mTcO4 delivered from a nebulizer connected to a dosimeter, and the lung fields were scanned with a gamma-camera. Right lung dose (RLD) was calculated as percentage of total dose. Intrapulmonary distribution was measured as penetration index (PI) (peripheral zone counts/central zone counts). Asthmatics had a significantly lower PI than normal subjects and there was a linear relationship between PI and baseline specific airway conductance (sGaw, p less than 0.001), and forced expiratory volume in one second (FEV1, p less than 0.05). After bronchodilatation with salbutamol (delta sGaw 101 +/- 31%, mean +/- SEM), PI increased from 0.73 +/- 0.11 to 1.09 +/- 0.15 (p less than 0.05); after bronchoconstriction with methacholine (delta sGaw 62.6 +/- 2.9%), PI decreased from 1.42 +/- 0.24 to 1.06 +/- 0.22 (p less than 0.05). Changes of PI were correlated with changes in sGaw and FEV1 (n = 20, p less than 0.001) but changes of RLD and changes in airway calibre were not. The distribution of inhaled aerosol, but not the dose, is largely dependent on airway calibre. The differences in PI between normal and asthmatic subjects may at best be explained by the differences in central airway calibre.

The Pollution Atmosphérique et Affections Respiratoires Chroniques (PAARC; Air Pollution and Chronic Respiratory Diseases) study provided the opportunity to examine the 25-yr mortality of 940 asthmatic adults drawn from a large population-based sample of 14,267 adults investigated during 1974–1976 in seven French cities.

Vital statistics were collected in 2001 for the whole population. Multivariate survival analysis was used to assess exact survival rates in asthmatics and nonasthmatics taking relevant confounders into account.

On average, the mortality rates obtained were 10.4 and 6.9 deaths·1,000 person-yrs⁻¹in asthmatics and nonasthmatics, respectively. On univariate analysis, asthma increased the relative risk (RR) of death by 1.48 (95% confidence interval (CI) 1.29–1.69). The association between asthma and death had an RR of 1.16 (95% CI 0.99–1.37) when age, sex, educational level, smoking habits, occupational exposure and forced expiratory volume in one second (FEV₁) were taken into account. FEV₁was an important contributive factor causing increased risk of death in both smokers and nonsmokers. For instance, in asthmatics, the numbers of deaths due to respiratory disease and cancer appeared excessive.

The present study suggests that asthmatics exhibit a higher risk of mortality.

This study was undertaken to investigate the reported association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and the expression of asthma-related symptoms. One hundred and eight children with asthma symptoms, aged 9-11 yrs, completed a 13 month longitudinal study. The children maintained a daily diary of respiratory symptoms and peak flow rates. When respiratory symptoms were reported an investigator was called and a nasal aspirate obtained. In total 292 episodes were reported. After the study 65 children provided samples when asymptomatic. The presence of infection was investigated by the polymerase chain reaction for C. pneumoniae and M. pneumoniae and C. pneumoniae secretory immunoglobulin A (IgA) was detected by amplified enzyme immunoassay. C. pneumoniae detections were similar between the symptomatic and asymptomatic episodes (23 versus 28%, respectively). Children who reported multiple episodes also tended to remain PCR positive for C. pneumoniae suggesting chronic infection (p< 0.02). C. pneumoniae-specific secretory-IgA antibodies were more than seven times greater in subjects who reported four or more exacerbations in the study compared to those who reported just one (p<0.02). M. pneumoniae was found in two of 292 reports and in two of 65 asymptomatic samples. In conclusion, chronic Chlamydia pneumoniae infection is common in schoolage children and immune responses to C. pneumoniae are positively associated with frequency of asthma exacerbations. We suggest that the immune response to chronic C. pneumoniae infection may interact with allergic inflammation to increase asthma symptoms. In contrast Mycoplasma pneumoniae was not found to be important in this study.

According to current guidelines, pulmonary arterial hypertension (PAH) is diagnosed when mean pulmonary arterial pressure (P̄_pa) exceeds 25 mmHg at rest or 30 mmHg during exercise. Issues that remain unclear are the classification ofP̄_pavalues <25mmHg and whetherP̄_pa>30 mmHg during exercise is always pathological.

We performed a comprehensive literature review and analysed all accessible data obtained by right heart catheter studies from healthy individuals to determine normalP̄_paat rest and during exercise. Data on 1,187 individuals from 47 studies in 13 countries were included. Data were stratified for sex, age, geographical origin, body position and exercise level.

P̄_paat rest was 14.0±3.3 mmHg and this value was independent of sex and ethnicity. RestingP̄_pawas slightly influenced by posture (supine 14.0±3.3 mmHg, upright 13.6±3.1 mmHg) and age (<30 yrs: 12.8± 3.1mmHg; 30–50 yrs: 12.9±3.0 mmHg; ≥50 yrs: 14.7±4.0 mmHg).P̄_paduring exercise was dependent on exercise level and age. During mild exercise,P̄_pawas 19.4±4.8 mmHg in subjects aged <50 yrs compared with 29.4±8.4 mmHg in subjects ≥50 yrs (p<0.001).

In conclusion, whileP̄_paat rest is virtually independent of age and rarely exceeds 20 mmHg, exerciseP̄_pais age-related and frequently exceeds 30 mmHg, especially in elderly individuals, which makes it difficult to define normalP̄_pavalues during exercise.