Giovanna Pisi

The airway neurogenic inflammation: clinical and pharmacological implications.

Bronchial airway microvasculature consists in a developed network of vessels, which plays an important role in normal homeostasis as well as in inflammatory airway processes. Its airway autonomic neural control includes cholinergic and adrenergic innervation, as well as nonadrenergic noncholinergic system. The nerve/vessel interplay is complex and not yet completely clarified. In response to inspired air conditions, the sensory nerves can recruit appropriate reflexes, which can induce different vascular processes, such as vasodilatation, vasoconstriction, plasma extravasation and exudation. Additionally, the stimulation of C fibres may result in an axon local reflex with antidromic conduction down afferent nerve collaterals and release of sensory neuropeptides, which in turn may act on the mucosal vasculature to promote vasodilatation and microvascular leakage. The neurogenic inflammation may play a key role in allergic diseases, such as asthma, as well as in COPD, a smoking-related disease. This review deals with the interactions of vessels and nerves within the airway mucosa under healthy conditions and in inflammatory diseases. The clinical and pharmacological implications are also described.

Assessment of Breathlessness Perception by Borg Scale in Asthmatic Patients: Reproducibility and Applicability to Different Stimuli

In asthmatics, the score of bronchoconstriction-associated breathlessness at 20% fall in forced expiratory volume at first second (FEV1) evaluated on a Borg scale (PS20) is a tool successfully used to measure the perception of symptoms. This prospective laboratory study evaluated the applicability of PS20 to assess the breathlessness induced by ultrasonically nebulized distilled water (UNDW) and methacholine (M) and its reproducibility. Twenty-two mild and clinically stable asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated by linear interpolation of the last two points of the perception/fall in FEV1 curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did not differ and were respectively 1.82 ± 1.85 and 2.03 ± 1.86. They were significantly related (rs = 0.63; p<0.01) and the bias between PS20 UNDW and PS20 M was –0.21 with the limits of agreement ranging from –3.2 to 3.6. The intraclass correlation coefficient for repeated measurement of PS20 M was 0.82; the bias between the two measurements was 0.2 with the limits of agreement ranging from –2.8 to 3.2. All patients had a measurable breathlessness perception degree on a Borg scale during both distilled water challenges and methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness perception were also similar for both stimuli. In addition, PS20 showed a good reproducibility and this allows the serial evaluation of patients breathlessness perception by this technique in clinical settings and in the physiology laboratory.

The Walking Capacity Assessment in the Respiratory Patient

Exercise testing is commonly used in respiratory patients to assess their degree of disability, prognosis for survival, presence of exercise-induced hypoxemia and response to treatment. Recently, simple exercise tests, which are based on walking, have been developed and are increasingly being used both for clinical and research purposes. The 6-min walk test (6-MWT) is the most widely used and simply consists in the measurement of the distance walked in 6 min. The 6-MWT is self-paced and differs from the shuttle walking test, which is externally paced via a recorded metronome and entails incrementally faster speeds. Although the field walking tests do not require complex equipment, they can provide reliable and useful clinical information. This review deals with the validity, reliability and interpretation of these walking tests in the assessment of patients with chronic respiratory disease.

The IGF system and cytokine interactions and relationships with longitudinal growth in prepubertal patients with cystic fibrosis

Objective  Growth delay is a feature of patients with cystic fibrosis (CF). CF is a condition characterized by chronic inflammation that has been shown to modify the IGF system, which is essential for normal growth, and is related to pulmonary function in CF patients. We aimed to verify whether circulating levels of tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, insulin and the IGF system were related and/or had relationships with linear growth in children with CF.

Flying with respiratory disease.

Patients with respiratory diseases may be at risk during flight because at cruising altitude an important hypobaric hypoxia may occur. The only absolute contraindications to flying in these patients are pneumothorax, bronchogenic cyst and severe pulmonary hypertension. In order to evaluate the risks related to air travel in patients with respiratory diseases, an evaluation of their fitness to fly, including the hypoxia altitude simulation test, is required. The fitness to fly evaluation can identify patients requiring supplemental oxygen during flight which is provided by most airlines when prescribed by the passenger’s physician. This review deals with the cardiorespiratory effects of flight, the risks associated with respiratory diseases during air travel and the procedures to follow in order to assess fitness to fly in patients with respiratory disorders.

Overweight is Associated with Airflow Obstruction and Poor Disease Control but Not with Exhaled Nitric Oxide Change in an Asthmatic Population

Background: The role of an elevated body mass index (BMI) in asthma remains controversial. Objectives: To investigate the relationship between overweight (BMI >25 and ≤30), lung function, disease control, and airway inflammation in an asthmatic population. Methods: We consecutively studied 348 patients (age 43 ± 16 years; 211 females). In all patients, BMI, spirometry, the Asthma Control Test (ACT), and fractional exhaled nitric oxide (FeNO; ppb) were measured. Results: One hundred forty-five patients were overweight and, as compared to those with normal BMI, had lower values of FVC, FEV1, and FEV1/FVC and of FEF25–75 even when normalized for FVC (p < 0.05 for each comparison). The ratio between the number of patients with well-controlled asthma (ACT ≥20) and that of patients with poorly controlled asthma (ACT < 20) was significantly lower in overweight patients (1.07 vs. 1.84; χ2 = 6.030, p < 0.01). In overweight patients, the odds ratio of uncontrolled asthma expressed by logistic regression analysis was 1.632 (95% CI = 1.043–2.553), independently of gender, atopy, smoking habit, and inhaled steroid therapy. No difference was observed in FeNO values between overweight and normal weight patients (27.7 ± 2.3 vs. 27.9 ± 2.2 ppb). Conclusions: Our results show that, in an asthmatic population, overweight is associated with airflow obstruction and poor disease control but not with FeNO change. The findings of the present study support the view that other factors besides airway inflammation alone may explain the relationship between asthma and an elevated BMI.

Short-Term Effects of High-Frequency Chest Compression and Positive Expiratory Pressure in Patients With Cystic Fibrosis

Background Cystic fibrosis patients require daily airway clearance therapies. The primary objective of this study was to compare the short-term efficacy of high-frequency chest compression and positive expiratory pressure mask on expectorated sputum, pulmonary function, and oxygen saturation in patients with CF hospitalized for an acute pulmonary exacerbation. Methods A controlled randomized cross-over trial with 24 hours between treatments was used. Thirty-four CF patients (26 ± 6.5 years) were included in the study. Before and 30 minutes after each treatment were recorded: pulmonary function testing, oxygen saturation, and perceived dyspnea. Preference for the two devices was assessed. Results No statistically significant difference between high-frequency chest compression and positive expiratory pressure mask was found in sputum production and in lung function testing. A reduction in SpO2 was found after positive expiratory pressure mask (98 ± 1.0% versus 97 ± 1.2%; P < 0.001). Both treatments induced a statistically significant increase in Borg scale for dyspnea without differences between them. Patients reported greater satisfaction with positive expiratory pressure mask than with high-frequency chest compression (P < 0.001). Conclusion High-frequency chest compression and positive expiratory pressure mask have comparable short-term effects on expectorated sputum and lung function. Although positive expiratory pressure mask was associated with a lower SpO2, it was better tolerated than high-frequency chest compression. Keywords Airway clearance therapies; High-frequency chest compression; Sputum; Cystic fibrosis

Mepolizumab in the treatment of severe eosinophilic asthma

IL-5 is crucial in the pathogenesis and evolution of eosinophilic asthma. Mepolizumab is a high-affinity humanized monoclonal antibody of the IgG1/k subtype that inhibits the binding of IL-5 to its receptor expressed on eosinophils, thereby inducing significant reduction in eosinophil circulation, as well as asthma exacerbations and corticosteroid treatment. This review deals with the currently available studies of mepolizumab in the treatment of patients with severe eosinophilic asthma.

HMGB1 Is Increased by CFTR Loss of Function, Is Lowered by Insulin, and Increases In Vivo at Onset of CFRD

CONTEXT Cystic fibrosis-related diabetes (CFRD) is associated with worsening of inflammation and infections, and the beginning of insulin treatment is debated. OBJECTIVES To verify high-mobility group box 1 protein (HMGB1) levels in CF patients according to glucose tolerance state, and analyze relationships with insulin secretion and resistance. To verify, in an in vitro model, whether HMGB1 gene expression and protein content were affected by insulin administration and whether these changes were dependent on CF transmembrane conductance regulator (CFTR) loss of function. PATIENTS AND METHODS Forty-three patients in stable clinical conditions and 35 age- and sex-matched controls were enrolled. Glucose tolerance was established in patients based on a 5 point oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FGIR), HOMA-IR index, whole-body insulin sensitivity index (WIBISI), and the areas under the curve for glucose (AUCG) and insulin (AUCI) were calculated. HMGB1 was assayed in serum, in cell lysates and conditioned media using a specific ELISA kit. For the in vitro study we used CFBE41o- cells, homozygous for the F508del mutation, and 16HBE14o- as non-CF control. HMGB1 gene expression was studied by real-time RT-PCR. Cells were stimulated with insulin at 2.5 and 5 ng/mL. The CFTR inhibitor 172 and CFTR gene silencing were used to induce CFTR loss of function in 16HBE14o- cells. RESULTS HMGB1 levels were increased at onset of CFRD (5.04 ± 1.2 vs 2.7 ± 0.3 ng/mL in controls; P < .05) and correlated with FGIR (R = +0.43; P = .038), and AUCI (R = +0.43; P = .013). CFTR loss of function in the 16HBE14o- cells increased HMGB1 and was lowered by insulin. CONCLUSION HMGB1 was increased in CF patients with deranging glucose metabolism and showed relationships with indexes of glucose metabolism. The increase in HMGB1 was related to CFTR loss of function, and insulin lowered HMGB1. Further research is required to verify whether HMGB1 could potentially be a candidate marker of onset of CFRD and to establish when to start insulin treatment.

Inhaled beclometasone dipropionate/formoterol fumarate extrafine fixed combination for the treatment of asthma

ABSTRACT Inhaled therapy is often considered the cornerstone of asthma management and international guidelines recommend combination therapy of inhaled corticosteroids (ICS) and long-acting-beta2-agonists (LABA) in a large proportion of asthmatic patients. The effectiveness of ICS/LABA is dependent on the correct choice of device and proper inhalation technique, this influences drug delivery and distribution along the bronchial tree, including the most peripheral airways. The fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/FF) is the only extrafine formulation available in pressurized metered dose inhaler (pMDI) and in dry powder inhaler (DPI). Here, we focus on the recent significant advances regarding BDP/FF fixed combination for the treatment of asthma.