Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

Impact of the UK lockdown on people at risk of COPD.

Impact of the UK lockdown on early COPD https://bit.ly/3laMsmi.

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort.

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach.

INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD.

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen). This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 µg once daily or SFC 50/500 µg twice daily. Patients had been receiving SFC 50/500 µg for ≥3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV1) after 12 weeks (non-inferiority margin of 0.06 L). The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45-26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George's Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected. This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 µg with no efficacy loss.

Treating Moderate-to-Severe Allergic Asthma with a Recombinant Humanized Anti-IgE Monoclonal Antibody (Omalizumab).

Bronchial asthma is a chronic inflammatory disease of the airways which is recognized as a highly prevalent health problem in both the developed and the developing world, with significant human and economic consequences.Allergy is acknowledged as a major risk factor for asthma. The pathogenetic aspects of allergic asthma are characterized by airway inflammation with infiltration of mast cells, basophils, eosinophils, monocytes and T helper type 2 lymphocytes, along with the isotype switching of B cells to generate immunoglobulins of the immunoglobulin E (IgE) class. Increased asthma severity is not only associated with recurrent hospitalization and increased mortality but also with higher social costs.Inhaled corticosteroids are the standard anti-inflammatory medication and are effective for most asthma patients, but there is a substantial number of asthmatics who remain symptomatic even after receiving treatment with inhaled corticosteroids and long-acting beta(2)-adrenoceptor agonists (beta(2)-agonists), and sometimes are in need of systemic corticosteroids to control the disease. These patients account for about 50% of the healthcare costs of asthma.New treatment options more specifically targeting the pathophysiologic events causing development of asthma are therefore required in these patients.A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference with the action of IgE and prevention of subsequent IgE-mediated responses.Omalizumab is a humanized recombinant monoclonal anti-IgE antibody developed for the treatment of allergic diseases, with clear efficacy in adolescent and adult patients with moderate-to-severe allergic asthma. This non-anaphylactogenic anti-IgE antibody inhibits IgE functions by blocking free serum IgE and inhibiting their binding to cellular receptors. Omalizumab therapy is well tolerated and significantly improves symptoms and disease control, and reduces asthma exacerbations and the need to use high dosages of inhaled corticosteroids. Moreover, omalizumab improves quality of life of patients with severe persistent allergic asthma that is inadequately controlled by currently available asthma medications. In conclusion, omalizumab may fulfill an important need in patients with moderate-to-severe asthma inadequately controlled with inhaled corticosteroids +beta(2)-agonists.

Variability of specific airway resistance in patients with laryngeal hemiplegia.

OBJECTIVES: This study was designed to analyze whether respiratory flows and specific airway resistance (sRaw) depend on the degree of breathiness and on the position of the paralyzed vocal fold in laryngeal hemiplegia. METHODS: We performed a prospective study involving 55 patients affected by laryngeal hemiplegia. RESULTS: The paralyzed fold was in an intermediate position in 18 cases and in a paramedian position in 37. Breathiness was estimated with the GRBAS scale, and the patients were divided into four groups: B0 (12 patients), B1 (14), B2 (16), and B3 (13). Spirometry was used to measure the flow-volume loop, and body plethysmography was used to measure the sRaw at increasing respiratory frequencies (30 +/- 5, 60 +/- 5, and 90 +/- 5 breaths per minute). The mean inspiratory flows (PIF, FIF50) were lower than predicted (<80%) in all four groups; there was no significant intergroup difference. In all four groups, the mean FEF5o/FIF50 ratio was >1, as is typical of variable extrathoracic obstruction. The mean sRaw values increased with respiratory frequency, and the increase was higher in group B3, although the values varied widely. The frequency-dependent increase in the sRaw value was not significantly related to the degree of breathiness, nor to the position of the paralyzed fold. Furthermore, Spearman's coefficient did not reveal any correlation between the sRaw values and inspiratory flows, showing that plethysmography and spirometry explore different aspects of airway function. CONCLUSIONS: Respiratory flows and sRaw are not significantly influenced by either the degree of breathiness or the position of the paralyzed vocal fold.

High levels of interleukin-6 in the exhaled breath condensate of patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the respiratory tract. METHODS: We investigated the presence of interleukin-6 (IL-6: a cytokine secreted by monocytes/macrophages, T cells, B cells, fibroblasts, bone marrow stromal cells, keratinocytes and endothelial cells) in the exhaled breath condensate of 16 exsmokers with moderate COPD, 12 healthy non-smokers. IL-6 was measured by means of a specific enzyme immunoassay. RESULTS: IL-6 levels were detectable in all of the subjects, but were higher in the COPD patients (8.0 +/- 0.1 pg/ml; P < 0.0001) than in the healthy non-smokers (4.9 +/- 0.2 pg/ml) with a correlation in this group between age and IL-6 levels (r = 0.597; P < 0.05). CONCLUSIONS: The increased IL-6 levels in exhaled breath condensate may reflect airway inflammation in patients with COPD.

Spirometric and plethysmographic assessment of upper airway obstruction in laryngeal hemiplegia.

Laryngeal hemiplegia (LH) is the most common disorder of laryngeal motility. It is deemed not to cause obstruction of the upper airway; in fact, the main symptoms are dysphonia and breathiness, and respiratory impairment is not commonly reported. The aim of this study was to objectively assess upper airway patency in 41 patients affected by LH (mean age, 54.4 +/- 15.2 years; 27 female) and 30 controls (mean age, 50.0 +/- 16.1 years; 19 female) by means of flow-volume loop spirometry and body plethysmography to measure specific airway resistance (sRaw) at increasing respiratory frequencies. The causes of LH were cervical surgery (28), tumor infiltration (5), and unexplained (8). None of the patients or controls was affected by lower airway disease. Spirometry showed that the patients had inspiratory flows (PIF, FIF50) significantly lower than those of the controls (p < .0001), whereas the expiratory flows (FEV1, FEF50) were normal, with the exception of peak expiratory flow (PEF), which was reduced, especially in female patients. The mean FEF50/FIF50 ratio (about unity in the normal subjects) was >1, as is typical of variable extrathoracic obstruction. Plethysmography showed that the values of sRaw of the LH group were not statistically different from those of the controls at 30 +/- 5 breaths per minute, but they progressively and significantly increased at 60 +/- 5 (p < .01) and 90 +/- 5 breaths per minute (p < .002), whereas no significant sRaw change was observed in the controls. These results show that LH causes obstruction of the upper airway that can be assessed and quantified by means of spirometry and body plethysmography. A dynamic narrowing due to inspiratory medialization of the paralytic vocal fold and flow turbulence during hyperventilation seem to be the causes of patency impairment. The flow-volume loop is an excellent, inexpensive, and easily available means of functionally evaluating upper airway obstruction, but some patients have difficulty in performing an inspiratory test that requires maximal effort, and the flow reduction during forced ventilation may be partially due to the effort dependency of the tests themselves. Plethysmographic assessment of airway resistance may be a valid alternative or complement, as it reveals an increase in sRaw at increasing respiratory frequencies.