Author: E. Garcia-Pachon

Author: V. Brusasco

Authors: A. Bush; C. Hogg

Authors: J. G. Ayres; B. Forsberg; I. Annesi-Maesano; R. Dey; K. L. Ebi; P. J. Helms; M. Medina-Ramón; M. Windt; F. Forastiere

Climate change will affect individuals with pre-existing respiratory disease, but the extent of the effect remains unclear.

The present position statement was developed on behalf of the European Respiratory Society in order to identify areas of concern arising from climate change for individuals with respiratory disease, healthcare workers in the respiratory sector and policy makers. The statement was developed following a 2-day workshop held in Leuven (Belgium) in March 2008.

Key areas of concern for the respiratory community arising from climate change are discussed and recommendations made to address gaps in knowledge. The most important recommendation was the development of more accurate predictive models for predicting the impact of climate change on respiratory health.

Respiratory healthcare workers also have an advocatory role in persuading governments and the European Union to maintain awareness and appropriate actions with respect to climate change, and these areas are also discussed in the position statement.

Authors: A. K. Simonds; D. K. Sokol

Pandemics and acute emergencies raise pressing medical, ethical and organisational challenges. These include global governance, priority setting, triaging of patients, allocation of scarce resources and restricting individual liberty in the interests of public health. We will focus particularly on an issue of direct relevance to all respiratory team members, i.e. what is the duty of the healthcare worker to continue working in the face of personal risk, and draw lessons from guidelines, ethical considerations, past pandemics and evolving experience with H1N1 swine influenza.

Authors: E. G. Tzortzaki; N. M. Siafakas

Chronic obstructive pulmonary disease (COPD) is generally thought to depend on an aberrant immune response to a noxious or infectious agent, which may cause chronic inflammation. However, the initiation of this abnormal response is not fully understood. Here, we propose a new hypothesis for the beginning of COPD, that the immune response to inhaled agents, mainly cigarette smoke, is directed toward the airway epithelium, due to oxidative DNA damage of the lung epithelial barrier cells (LEBCs). The steps of this model are as follows. 1) Cigarette smoke induces oxidative DNA damage of LEBCs. 2) The acquired mutations are expressed at the microsatellite DNA level of LEBCs. 3) The altered LEBCs are recognised by dendritic cells (DCs) as “nonself”. DCs travel, with the new information, to the lymph nodes, presenting it to the naïve T-lymphocytes. 4) A predominant CD8+ cytotoxic T-lymphocyte proliferation occurs. The CD8+ cells, by releasing perforin and granzymes, attack the altered LEBCs activating cell death cascades.

Obviously, the above scenario needs further experimental exploration. However, it is an attractive model for the initiation of the abnormal inflammation in COPD, comprising oxidative DNA damage of LEBCs and host immune response.

Authors: R. Dales; L. Chen; A. M. Frescura; L. Liu; P. J. Villeneuve

Urban air pollution has been associated with morbidity but little information exists on how it affects diurnal variation of lung function in children with asthma. The purpose of this study was to investigate the acute effects of traffic-related pollution on lung function among children with asthma.

We recorded morning and evening forced expiratory volume in 1 s (FEV1) for 28 consecutive days in 182 elementary schoolchildren with physician-diagnosed asthma, and monitored ambient hourly air pollution concentrations.

An interquartile range (IQR) increase (6.0 μg·m⁻³) in the previous 24-h (20:00 h to 20:00 h) mean concentration of fine particulate matter 2.5 μm in diameter (PM2.5) was associated with a 0.54% (95% confidence interval (CI) 0.06–1.02) decrease in bedtime FEV1 (p = 0.027). This association persisted in two-pollutant models with ozone, nitrogen dioxide and sulphur dioxide. An IQR increase in mean daytime (08:00 h to 20:00 h) PM2.5 of 6.5 μg·m⁻³ was associated with a 0.73% (95% CI 0.10–1.37) decrease in FEV1 over the course of the day expressed as 100×(FEV1 bedtime − FEV1 morning)/FEV1 morning (p = 0.024).

This study suggests that, in children with asthma, relatively low concentrations of urban air pollution worsen lung function over a short period of time, even within a day. Of the pollutants measured, PM2.5 appears to be the most important.

Authors: G. Deslee; J. C. Woods; C. M. Moore; L. Liu; S. H. Conradi; M. Milne; D. S. Gierada; J. Pierce; A. Patterson; R. A. Lewit; J. T. Battaile; M. J. Holtzman; J. C. Hogg; R. A. Pierce

Alveolar elastic fibres are key targets of proteases during the pathogenesis of chronic obstructive pulmonary disease (COPD). In the current study, we hypothesised that a response to injury leads to enhanced alveolar elastin gene expression in very severe COPD.

Lung samples obtained from 43 patients, including 11 with very severe COPD (stage 4), 10 donors, 10 with moderate/severe COPD (stage 2–3) and 12 non-COPD subjects, were analysed for elastin mRNA expression by real-time RT-PCR and in situ hybridisation. Alveolar elastic fibres were visualised using Hart's staining of sections of frozen inflated lungs obtained from 11 COPD stage 4 patients and three donor lungs.

Compared with donors, non-COPD and stage 2–3 COPD, elastin mRNA expression was significantly increased in very severe COPD lungs (12-fold change), and localised in situ hybridisation induced elastin expression to alveolar walls. Compared with donors, alveolar elastic fibres also comprised a greater volume fraction of total lung tissue in very severe COPD lungs (p<0.01), but elastic fibre content was not increased per lung volume, and desmosine content was not increased.

The present study demonstrates enhanced alveolar elastin expression in very severe COPD. The efficiency of this potential repair mechanism and its regulation remain to be demonstrated.

Authors: P-O. Bridevaux; M. W. Gerbase; C. Schindler; D. Felber Dietrich; I. Curjuric; J. Dratva; U. Ackermann-Liebrich; N. M. Probst-Hensch; J-M. Gaspoz; T. Rochat

Systemic inflammation may mediate the association between chronic obstructive pulmonary disease (COPD) and extrapulmonary comorbidities. We measured high-sensitivity C-reactive protein (hs-CRP) in COPD and quantified the effect modification by body weight change and sex.

Using data from the Swiss study on Air Pollution and Lung Diseases in Adults (SAPALDIA; n = 5,479) with measurements of forced expiratory volume in 1 s (FEV1), body weight and hs-CRP, we examined the association of hs-CRP and categories of body weight change (lost weight and weight gained 0–5%, 5–9%, 9–14% and >14%) with fast FEV1 decline.

hs-CRP was elevated both in association with fast FEV1 decline and body weight gain. Subjects with fast FEV1 decline and weight gain (>14%) had higher hs-CRP (2.0 mg·L⁻¹ for females versus 1.6 mg·L⁻¹ for males). After adjustment for age, smoking, physical activity, hormonal therapy and diabetes, elevated hs-CRP (>3 mg) was found to be more likely in subjects with fast FEV1 decline (ORmales 1.38, ORfemales 1.42) and in those with weight gain >14% (ORmales 2.04, ORfemales 4.51).

The association of weight gain and fast FEV1 decline predicts a higher level of systemic inflammation. Since the effect of weight gain on systemic inflammation is larger in females than in males, weight gain may be a risk factor for extrapulmonary comorbidities in females with COPD.

Authors: L. Puente-Maestu; F. Villar; J. de Miguel; W. W. Stringer; P. Sanz; M. L. Sanz; J. García de Pedro; Y. Martínez-Abad

The endurance time during constant high work-rate exercise (tLIM) is used to assess exercise capacity in patients with chronic obstructive pulmonary disease and as an outcome measure for pulmonary rehabilitation. Our study was designed to establish the minimum clinically important difference for the tLIM.

tLIM was measured in 105 patients (86 males) before and after an 8-week outpatient pulmonary rehabilitation programme. Subjects were asked to identify, from a five-point Likert scale, the perceived change in their exercise performance immediately upon completion of the exercise tests. The scale ranged from “better” to “worse”.

The mean±sd age was 64±5 yrs, forced expiratory volume in 1 s (FEV1) 47±10% and FEV1/forced vital capacity 54.7±16.3%. Baseline tLIM at 75% of the peak work rate was 397±184 s, which increased by 62±63% after rehabilitation. In subjects who felt their exercise tolerance was “slightly better”, the mean improvement was 34% in the relative improvement over the baseline value (95% CI 29–39)% or 101 (86–116) s compared with 121 (109–134)% in those who reported that their exercise tolerance was “better” and 8 (2–14)% in those who felt their exercise tolerance was “about the same”.

Minimum clinically important improvement for tLIM averaged ∼33% of baseline. Patients were able to distinguish at least one further additional level of benefit at 120% of baseline.

Authors: A. M. Wood; R. M. Harrison; S. Semple; J. G. Ayres; R. A. Stockley

The aim of this study was to determine whether long-term air pollution exposure is associated with clinical phenotype in α1-antitrypsin deficiency.

In total, 304 PiZZ subjects underwent full lung function testing and quantitative high-resolution computed tomography to identify the presence and severity of the disease. Mean annual air pollutant data for 2006 was matched to the location of patients' houses and used in regression models to identify phenotypic associations with pollution, controlling for covariates. Relative trends in pollution levels were assessed to validate use of a single year's data to indicate long-term exposure.

Pollutant levels correlated significantly with one another, with higher levels of primary particles, SO2 and NO2 being associated with lower ozone levels. Regression models showed that estimated higher exposure to ozone was associated with worse gas transfer and more severe emphysema. Regression parameters suggested that significance from other pollutants was due to collinearity with ozone. The 2006 pollutant levels showed linear relationships with cumulative years, thus validating the model.

Higher exposures to ozone may be associated with worse respiratory status in α1-antitrypsin deficiency, identifying a group susceptible to ambient air pollution.

Authors: P. Brand; M. Schulte; M. Wencker; C. H. Herpich; G. Klein; K. Hanna; T. Meyer

Individuals with α1-antitrypsin (AAT) deficiency and cystic fibrosis (CF) have a protease–antiprotease imbalance in their lungs, which leads to early onset progressive lung disease. Inhalation of AAT may restore protective levels in the lungs. This study aimed to determine the efficiency of delivering AAT using a novel inhalation device in subjects with AAT deficiency and CF compared with healthy subjects.

In total, 20 subjects (six healthy, seven with AAT deficiency and seven with CF) inhaled ∼70 mg of radiolabelled active AAT, with controlled breathing patterns adjusted to lung function. Post-inhalation, total and regional lung deposition and extrathoracic deposition of radiolabelled AAT were measured.

Total lung deposition of AAT was ∼70% of the filling dose. The magnitude of deposition was similar in all treatment groups, with no adverse effect on lung function or any influence of disease severity on total lung deposition.

Inhalation with controlled breathing patterns using the AKITA² device (lung function adapted) leads to high total lung deposition regardless of the degree of lung function impairment. Delivery of large amounts of AAT was achieved in a short period of time. This device may be an ideal option for aerosol therapy.

Authors: M. P. Murray; J. L. Pentland; K. Turnbull; S. MacQuarrie; A. T. Hill

This study explored the utility of sputum colour in clinically stable patients with bronchiectasis. Interpretation of sputum colour between the doctor and the patient was reliable (intraclass correlation coefficient 0.83 (95% confidence interval 0.76–0.89). Sputum colour predicted bacterial colonisation (5% in mucoid sputum; 43.5% in mucopurulent sputum; 86.4% in purulent sputum; p<0.0001). On multivariate logistic regression analysis, independent factors associated with purulent sputum were bacterial colonisation, varicose or cystic bronchiectasis, forced expiratory volume in 1 s <80% predicted and diagnosis of bronchiectasis aged <45 yrs.

Authors: D. Adler; J. Gonzalez-Bermejo; A. Duguet; A. Demoule; F. Le Pimpec-Barthes; A. Hurbault; C. Morélot-Panzini; T. Similowski

High cervical spinal cord injuries induce extreme handicap and tactile isolation. Tracheotomised tetraplegic patients are also bound to be olfaction deprived. By restoring negative pressure inspiration, diaphragm pacing (DP) should improve olfaction.

We tested olfaction in 10 consecutive tetraplegics during positive pressure mechanical ventilation and DP, using the University of Pennsylvania Smell Identification Test (UPSIT). Quality of life was assessed using the Satisfaction with Life Scale (SWLS). Self-perceived benefits of DP were studied using an in-house questionnaire.

Olfaction was very poor during positive pressure mechanical ventilation (UPSIT, mean±sd 17.1±6.4, anosmia or severe microsmia). It improved during DP (35.2±1.9, normosmia or mild microsmia; p<0.0001) and SWLS was 18.5±4.2. Nine patients stated that DP had improved their quality of life. This was driven by better mobility (ranked first), improved self-image and relationships with others (ranked second), improved olfaction and better feeling of security (both ranked third).

Improved olfaction is among the benefits of DP and should be mentioned to patients considered for this therapy. Furthermore, attention to olfaction is warranted in tracheotomised ventilator-dependent patients, as a putative path towards improvement of quality of life.

Authors: M. J. Overbeek; M. C. Vonk; A. Boonstra; A. E. Voskuyl; A. Vonk-Noordegraaf; E. F. Smit; B. A. C. Dijkmans; P. E. Postmus; W. J. Mooi; Y. Heijdra; K. Grünberg

Systemic sclerosis-associated pulmonary arterial hypertension (SScPAH) has a worse prognosis and response to pulmonary arterial hypertension (PAH) therapy than idiopathic PAH (IPAH). These differences have not yet been explained. Knowledge concerning histological pulmonary vasculopathy in SScPAH is limited in contrast to IPAH. Therefore, we explored patterns of vasculopathy in SScPAH compared with IPAH.

Parameters of vasculopathy were assessed from lung tissue of eight PAH patients with limited cutaneous systemic sclerosis and 11 IPAH patients. Lung tissue was obtained at autopsy (n = 15), explantation (n = 3) and biopsy (n = 1).

Pulmonary arterial/arteriolar intimal fibrosis was identified in all SScPAH patients and in three IPAH patients (p = 0.003). Fibrosis of pulmonary veins/venules was found in all SScPAH patients and in three IPAH patients (p = 0.003). In four SScPAH patients, fibrosis of veins/venules was focal and associated with capillary congestion as in pulmonary veno-occlusive disease (PVOD). Of the IPAH patients, 10 had unequivocal evidence of plexogenic arteriopathy compared with none of the SScPAH patients (p = 0.001).

SScPAH is characterised by small vessel intimal fibrosis, which is associated with a PVOD-like pattern in some cases. This might explain its different clinical behaviour from IPAH. Small vessel intimal fibrosis may provide clues to elucidation of differences in pathogenetic mechanisms between the groups.

Authors: R. P. Young; R. J. Hopkins; T. Christmas; P. N. Black; P. Metcalf; G. D. Gamble

Chronic obstructive pulmonary disease (COPD) is a common comorbid disease in lung cancer, estimated to affect 40–70% of lung cancer patients, depending on diagnostic criteria. As smoking exposure is found in 85–90% of those diagnosed with either COPD or lung cancer, coexisting disease could merely reflect a shared smoking exposure. Potential confounding by age, sex and pack-yr smoking history, and/or by the possible effects of lung cancer on spirometry, may result in over-diagnosis of COPD prevalence.

In the present study, the prevalence of COPD (pre-bronchodilator Global Initiative for Chronic Obstructive Lung Disease 2+ criteria) in patients diagnosed with lung cancer was 50% compared with 8% in a randomly recruited community control group, matched for age, sex and pack-yr smoking exposure (n = 602, odds ratio 11.6; p<0.0001).

In a subgroup analysis of those with lung cancer and lung function measured prior to the diagnosis of lung cancer (n = 127), we found a nonsignificant increase in COPD prevalence following diagnosis (56–61%; p = 0.45). After controlling for important variables, the prevalence of COPD in newly diagnosed lung cancer cases was six-fold greater than in matched smokers; this is much greater than previously reported.

We conclude that COPD is both a common and important independent risk factor for lung cancer.

Authors: G. B. Migliori; B. Eker; M. D. Richardson; G. Sotgiu; J-P. Zellweger; A. Skrahina; J. Ortmann; E. Girardi; H. Hoffmann; G. Besozzi; N. Bevilacqua; D. Kirsten; R. Centis; C. Lange

Linezolid is used to treat patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-tuberculosis (TB) cases, although clinical data on its safety, tolerability and efficacy are lacking.

We performed a retrospective, nonrandomised, unblinded observational study evaluating the safety and tolerability of linezolid at 600 mg q.d. or b.i.d. in MDR/XDR-TB treatment in four European countries. Efficacy evaluation compared end-points of 45 linezolid-treated against 110 linezolid-nontreated cases.

Out of 195 MDR/XDR-TB patients, 85 were treated with linezolid for a mean of 221 days. Of these, 35 (41.2%) out of 85 experienced major side-effects attributed to linezolid (anaemia, thrombocytopenia and/or polyneuropathy), requiring discontinuation in 27 (77%) cases. Most side-effects occurred after 60 days of treatment. Twice-daily administration produced more major side-effects than once-daily dosing (p = 0.0004), with no difference in efficacy found. Outcomes were similar in patients treated with/without linezolid (p = 0.8), although linezolid-treated cases had more first-line (p = 0.002) and second-line (p = 0.02) drug resistance and a higher number of previous treatment regimens (4.5 versus 2.3; p = 0.07).

Linezolid 600 mg q.d. added to an individualised multidrug regimen may improve the chance of bacteriological conversion, providing a better chance of treatment success in only the most complicated MDR/XDR-TB cases. Its safety profile does not warrant use in cases for which there are other, safer, alternatives.

Authors: F. Scaglione; S. Esposito; S. Leone; V. Lucini; M. Pannacci; L. Ma; G. L. Drusano

Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes.

Only patients treated with aminoglycosides, fluoroquinolones, and β-lactams were evaluated. MICs were determined using standard National Committee for Clinical Laboratory Standards procedures. Antibiotics were assayed using validated high-performance liquid chromatographic methods. Pharmacokinetic/pharmacodynamic markers adopted were: aminoglycoside peak/MIC ratio ≥8 mg·L⁻¹; fluoroquinolone peak/MIC ≥10 mg·L⁻¹; β-lactam peak/MIC ≥4 mg·L⁻¹ and time that plasma levels remain above the MIC ≥70%.

638 patients with NP were included in the study. In 205 patients, both drug concentration and isolate MIC were available, while in other patients, used as controls, one or both parameters were lacking. For clinical outcome, the Acute Physiology and Chronic Health Evaluation II score (p<0.0001), the presence of combination therapy (p = 0.0014) and whether both MIC and drug concentration(s) were measured (p = 0.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the β-lactams (≤2 mg·L⁻¹; p<0.0001) and whether the second drug was a fluoroquinolone or aminoglycoside (fluoroquinolones were better than aminoglycosides; p = 0.0177), as well as whether both MIC and drug concentration(s) were measured (p = 0.02), affected the probability of eradication.

Measurement of drug concentrations and determination of pathogen MIC values with subsequent dose alteration significantly improves the probability of good clinical outcome and pathogen eradication in NP.

Authors: B. Thomas; A. Rutman; C. O'Callaghan

Ciliary function studies for the diagnosis of primary ciliary dyskinesia (PCD) are usually performed on nasal brush biopsy samples. It is not uncommon to find disrupted epithelial strips of tissue in these samples, and occasionally throughout a sample. The aim of the present study was to determine if cilia on disrupted ciliated epithelial edges beat with a normal pattern and frequency similar to that of cilia on undisrupted edges.

Nasal brush biopsy samples from 42 children in whom the diagnosis of PCD was excluded were assessed. The epithelial strips were categorised into five groups: intact undisrupted ciliated epithelial edge, ciliated epithelial edge with minor projections, ciliated epithelial edge with major projections, an isolated ciliated cell on an epithelial edge and single unattached ciliated cells. Ciliary beat frequency and beat pattern of 50 samples from each group were determined using high speed digital video microscopy.

The cilia on epithelial edges with varying degrees of disruption showed significantly reduced beat frequency and significantly increased dyskinesia compared with those on intact, undisrupted ciliated epithelial edges.

Ideally, the assessment of ciliary beat pattern and frequency for PCD diagnosis should only be performed on undisrupted ciliated edges.

Authors: T. Demoor; K. R. Bracke; T. Maes; B. Vandooren; D. Elewaut; C. Pilette; G. F. Joos; G. G. Brusselle

In chronic obstructive pulmonary disease (COPD), chronic inflammation is accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-α, crucial in secondary lymphoid organogenesis, may be involved in lymphoid neogenesis.

We examined cigarette smoke (CS)-induced pulmonary lymphoid neogenesis and inflammation in vivo in LTα knockout (LTα^-/-) and wild-type (WT) mice and studied the expression of lymphoid chemokines by lung fibroblasts in vitro.

T-cell numbers (in bronchoalveolar lavage fluid (BALF) and lungs) and lymphoid aggregate numbers were significantly higher in air-exposed LTα^-/- mice than in WT animals, and increased upon chronic CS exposure in both genotypes. In contrast, local immunoglobulin A responses upon chronic CS exposure were attenuated in LTα^-/- mice. CXC chemokine ligand (CXCL) 13 and CC chemokine ligand (CCL) 19 mRNA in total lung and CXCL13 protein level in BALF increased upon CS exposure in WT, but not in LTα^-/- mice. In vitro lymphotoxin-β receptor (LTβR) stimulation induced CXCL13 and CCL19 mRNA in WT lung fibroblasts. Furthermore, in vitro exposure to CS extract upregulated CXCL13 mRNA expression in WT, but not in LTβR^-/-, lung fibroblasts.

In this murine model of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19 in a LTαβ–LTβR-dependent fashion. However, LTα is not required for CS-induced pulmonary lymphocyte accumulation and neogenesis of lymphoid aggregates.

Authors: F-X. Blanc; C. Coirault; P. Oliviero; Y. Lecarpentier

The current study was designed to determine whether the nonspecific in vivo airway hyperresponsiveness of the inbred Fisher F-344 rat strain is associated with impaired spontaneous relaxation of airway smooth muscle.

Strips of the posterior portion of the trachea from 10 adult Fisher and 10 adult Lewis rats were electrically stimulated at pH 7.4, 2.5 mM Ca²⁺concentration, at 37°C. Both isotonic and isometric relaxations of tracheal smooth muscle (TSM) were investigated.

Half time for isotonic relaxation at preload was markedly prolonged in Fisher rats (8.33±3.21 s) compared with Lewis rats (3.53±0.54 s; p<0.001). Maximum lengthening velocity at preload and peak rate of isometric tension decline were significantly decreased in Fisher rats compared with Lewis rats. The ratio of shortening velocity to lengthening velocity at preload, as well as the ratio of the isometric peak rates of tension development to tension decline were higher in Fisher rat TSM than in Lewis rat TSM. These differences were associated with a six-fold higher expression of myosin light chain kinase in Fisher rats than in Lewis rats.

In Fisher rats, these results suggest that innate airway hyperresponsiveness is associated with both a reduced level and a slower rate of TSM spontaneous relaxation, promoting maintenance of airway constriction.

Authors: Y. Okayama; S. Okumura; H. Sagara; K. Yuki; T. Sasaki; N. Watanabe; M. Fueki; K. Sugiyama; K. Takeda; T. Fukuda; H. Saito; C. Ra

A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP) has been reported in the bronchial mast cells (MCs) of asthmatic subjects; however, the mechanism underlying the upregulation of TSLP mRNA and protein remains unknown.

FcεRI-mediated activation of human MCs upregulated TSLP mRNA expression by 5.2±2.9-fold, while activation of the MCs using lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h significantly enhanced the FcεRI-mediated TSLP mRNA expression (by 53.7±15.9-fold; p<0.05) and the amount of TSLP in the cell pellets increased significantly from 23.4±4.3 pg·mL⁻¹ to 121.5±3.7 pg·mL⁻¹ (p<0.0001). However, the released TSLP was rapidly degraded by proteases that were released by MCs. We identified the population of cells expressing TSLP in the lungs of 16 asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP-positive MCs in the total population of MCs was significantly increased in asthmatic airways (p<0.0001).

Thus, MCs are able to store TSLP intracellularly and to produce TSLP following aggregation of FcεRI in the presence of IL-4.

Authors: A. Barbato; F. Bertuola; C. Kuehni; M. Korppi; S. Kotecha; M. W. Pijnenburg; F. Ratjen; P. Seddon; A. Bush

The aim of this report is to describe the highlights of the European Respiratory Society annual congress in Berlin, Germany. The best abstracts in asthma and allergy, cystic fibrosis, respiratory infection, paediatric and neonatal intensive care, paediatric investigative techniques (in particular respiratory physiology and bronchoscopy) and respiratory epidemiology are presented and set in the context of the current literature.

Authors: N. Ambrosino; N. Carpenè; M. Gherardi

Neuromuscular diseases (NMD) may affect respiratory muscles, leading to respiratory failure. Studies show that long-term noninvasive mechanical ventilation (NIV) improves symptoms, gas exchange, quality of life and survival. NIV improved these parameters in muscular dystrophies and also in patients with amyotrophic lateral sclerosis without severe bulbar dysfunction. NIV should be started at the onset of nocturnal hypoventilation. In selected cases, NIV may be simpler, better accepted by patients and cheaper than invasive mechanical ventilation, but it cannot be used as an alternative. Tracheostomy may be preferred by patients unable to protect their airways and wishing to survive as long as possible, or by ventilator-dependent patients.

Glossopharyngeal breathing consists of taking air and propelling it into the lungs. Chest percussions and vibrations can help to mobilise airway secretions but they cannot substitute coughing. Manually assisted coughing requires substantial lung inflation through air stacking or deep lung insufflation, followed by an abdominal thrust with open glottis. The combination of mechanical in-exsufflation with an abdominal thrust is a mechanically assisted cough.

In conclusion, recent advances in respiratory care of NMD have improved prognosis and many caregivers have changed from a traditional noninterventional to a more aggressive, supportive approach.

Authors: P. G. Jorens; E. Van Marck; A. Snoeckx; P. M. Parizel

Nonthrombotic pulmonary embolism (NTPE) is defined as embolisation to the pulmonary circulation of different cell types (adipocytes, haematopoietic, amniotic, trophoblastic or tumour), bacteria, fungi, foreign material or gas. The purpose of this article is to describe the clinical signs, pathogenesis, diagnosis and treatment of the different NTPE subtypes.

The complex and diverse pathogenesis of different subtypes of emboli is subject to continuing speculation and is certainly far more complex than “simple” mechanical obstruction after embolisation of vascular thrombi. Nonthrombotic emboli may also lead to a severe inflammatory reaction both in the systemic and pulmonary circulation, as well as in the lung.

NTPE presents a formidable diagnostic challenge, as the condition often presents with very unusual and peculiar clinical signs that are frequently overlooked. They range from very dramatic acute presentations such as acute respiratory distress syndrome to signs observed late in the disease course. Pathological observations play a key role in the exact diagnosis, and sometimes carefully aspirated blood from the pulmonary artery or specific staining of cells recovered from bronchoalveolar lavage fluid may be helpful. Frequently, lung biopsies revealing severe granulomatous reaction or unfortunate post-mortem pathological investigations of pulmonary tissue are necessary to confirm the diagnosis. Here, we also aim to familiarise the reader with the atypical radiological features of NTPE. Thin-section computed tomography of the lungs showing peculiar radiographic findings, such as a feeding vessel, the so-called tree-in-bud pattern or the appearance of micronodules distributed at the termination of bronchovascular bundles, may be observed in certain forms of NTPE.

Increased awareness of NTPE as an underestimated cause of acute and chronic embolism, which may result in acute and chronic pulmonary hypertension, is needed. Despite the fact that detailed descriptions of several forms of NTPE have existed for nearly 100 years, well-designed trials have never been performed to evaluate therapy in the different subsets of these patients.

Authors: B. Gooptu; U. I. Ekeowa; D. A. Lomas

The severe, early onset emphysema that occurs in patients with circulating deficiency of α1-antitrypsin (α1-AT) attests to the importance of this protease inhibitor in maintaining lung parenchymal integrity. It has led to the powerful concept of protease:antiprotease balance being crucial to alveolar homeostasis.

Pathogenic mutations cause α1-AT to self-associate into polymer chains that accumulate intracellularly rather than proceeding along the secretory pathway. Polymerisation of α1-AT abolishes antiprotease activity and confers toxic gain-of-function effects. Since α1-AT is predominantly synthesised in the liver, where it does not play a major homeostatic role, the directly toxic effects of polymerisation are clearest here. However, data from molecular, cellular, animal and ex vivo studies indicate that intrapulmonary polymerisation of α1-AT and inflammatory positive feedback loops may augment the destructive effects of decreased antiprotease levels in the lung.

This review integrates the findings from these different approaches and highlights how multiple pathways may converge to give the severe, panacinar emphysema phenotype seen in α1-AT deficiency.

Authors: S. Ocak; M. L. Sos; R. K. Thomas; P. P. Massion

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets.

Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development.

Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone.

The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the “-omics” have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

Author: J. Escarrabill

Discharge support for the most seriously ill chronic obstructive pulmonary disease (COPD) patients is a key issue in minimising the impact of the acute episode and preventing future relapses.

Alternatives to hospitalisation are crucial in the cost minimisation of COPD care. However, besides efficiency, there are clinical reasons for promoting alternatives to conventional hospital admission. Hospital stay itself conveys a risk to patients.

The discharge process is a key element in the healthcare continuum. Hospital at home is a safe alternative to hospital admission, but it is not the only means of supporting discharge. Some home care schedules, mainly supported by nurses, have been proven to be good alternatives.

Home care is also useful in the prevention of hospital admission. Integrated care is a comprehensive response to the needs of severely affected COPD patients achieved through models of shared care utilising all relevant health providers and promoting self-management. The framework for integrated care is the so-called chronic care model, centred on the promotion of self-management, the holistic appraisal of the patient, the most appropriate design of healthcare delivery responding effectively to the needs of the patient and a good system of shared and accessible information.

Authors: S. El-Chemaly; A. Taveira-DaSilva; M. P. Stylianou; J. Moss

Authors: C. B. Cooper; W. J. Boscardin; J. R. Colthurst; E. C. Kleerup

Authors: R. M. Jones; A. Dawson; G. H. Jenkins; A. G. Nicholson; D. M. Hansell; N. K. Harrison

Authors: M. M. van der Eerden; W. G. Boersma

Authors: A. Aliverti; M. Quaranta; P. M. Calverley

Author: F. Madsen

Authors: D. P. Steinfort; D. F. Johnson; L. B. Irving

Author: A. R. Haas

Authors: L. Guilleminault; P. Carré; P. Diot