Somatically evoked cough responses help to identify patients with difficult-to-treat chronic cough: a six-month observational cohort study.

Background: Recently we identified in patients with chronic cough a sensory dysregulation via which the urge-to-cough (UTC) or coughing are evoked mechanically from "somatic points for cough" (SPCs) in the neck and upper trunk. We investigated the prevalence and the clinical relevance of SPCs in an unselected population of patients with chronic cough.

Methods: From 2018 to 2021, symptoms of 317 consecutive patients with chronic cough (233 females) were collected on four visits (V1-V4) 2 months apart at the Cough Clinic of the University Hospital in Florence (I).

Somatic points for cough and urge to cough in chronic coughers.

In patients with chronic cough and age-matched control subjects, we attempted to evoke coughing and/or an urge to cough (UTC) by finger pressure along the sternocleidomastoid and sternum, on the lower cervical or first dorsal vertebrae, the jugular notch as well as with maximum neck extension and flexion These mechanical actions were ineffective in controls but reproducibly evoked coughing or UTC in about 50% of chronic coughers; sternal and spinal responses were abolished temporarily by local cooling. The results may disclose a novel paradigm of cough sensitisation possibly involving central convergence of somatic and visceral neural stimuli.

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a well-known and widely accepted biomarker of airways inflammation that can be useful in the therapeutic management, and adherence to inhalation therapy control, in asthmatic patients. However, the multiple-flows assessment of FeNO can provide a reliable measurement of bronchial and alveolar production of NO, supporting its potential value as biomarker also in peripheral lung diseases, such as interstitial lung diseases (ILD). In this review, we first discuss the role of NO in the pathobiology of lung fibrosis and the technique currently approved for the measurement of maximum bronchial flux of NO (J'awNO) and alveolar concentration of NO (CaNO).

Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study.

Background: Cough is a common presenting symptom in patients with idiopathic interstitial pneumonia (IIP); it is often disabling, and lacks effective treatment. Studies in animals suggest that carcainium chloride, a quaternary derivative of the local anesthetic lidocaine, is able to inhibit experimentally induced cough by a mechanism of action distinct from that of lidocaine.

Objective: To determine the effectiveness of aerosolised carcainium chloride (VRP700) in controlling cough in patients with IIP.

Optimising Inhaled Pharmacotherapy for Elderly Patients with Chronic Obstructive Pulmonary Disease: The Importance of Delivery Devices.

Chronic obstructive pulmonary disease (COPD) is common in older people. Inhaled medications are the mainstay of pharmacological treatment of COPD, and are typically administered by handheld inhalers, such as pressurised metered-dose inhalers and dry powder inhalers, or by nebulisers. For each of the three major categories of aerosol delivery devices, several new inhalers have recently been launched, each with their own particularities, advantages and disadvantages.

The Clinical Value of Deflation Cough in Chronic Coughers With Reflux Symptoms.

Background: Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms.

Effect of an anti-reflux medical device in the control of deflation cough: A placebo-controlled comparative study with an antacid drug in chronic coughers.

Background: Deflation cough (DC), i.e. the cough-like expiratory expulsive efforts evoked by maximal lung emptying, is partially inhibited by prior intake of an antacid.

A crossover randomized comparative study of zofenopril and ramipril on cough reflex and airway inflammation in healthy volunteers.

Background: Persistent dry cough is a well known unwanted effect of Angiotensin-Converting Enzyme inhibitors (ACE-i). Animal studies have shown that the ACE-i zofenopril has a less tussigenic effect compared to the widely used ACE-i ramipril. The aim of this study was to compare cough sensitivity to inhaled tussigens, as well as spontaneous cough in response to the administration of zofenopril and ramipril in healthy volunteers; pharmacokinetic (PK) data of both zofenopril and ramipril, as well as their respective active forms, zofenoprilat and ramiprilat, was also collected.

New inhaler devices - the good, the bad and the ugly.

Drug delivery to the lungs is an effective way of targeting inhaled therapeutic aerosols and treating obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In the past 10 years, several new drugs for the management of asthma and COPD have been marketed and more are under development. These new therapeutic respiratory drugs have been furthered by innovations in all categories of pulmonary drug delivery systems to ensure optimal aerosolisation performance, consistency in efficacy and satisfactory patient adherence.

Respiratory rate assessments using a dual-accelerometer device.

Monitoring of respiration-related thoracic movements may be useful to assess respiratory rate (RR) objectively. RR was measured during spontaneous breathing, voluntarily modified breathing, and exercise hyperpnoea in normal subjects via visual inspection, spirometry and a pair of accelerometers positioned on the torso. Spirometric and accelerometric values of RR recorded during relaxed breathing were (mean±SD) 21.

Inhaler technique and patient's preference for dry powder inhaler devices.

Inhaled therapy has a central place in the management of obstructive lung diseases, but a large number of patients are unable to use their inhalers correctly with a consequent reduction in therapeutic benefit. Correct use of inhalers is, therefore, crucial for efficient therapy, and acceptance of the device can improve patients' compliance. The choice of the most appropriate inhaler for a given patient is often not straightforward.

Different respiratory behaviors disclosed by induced bronchoconstriction in mild asthma patients.

Respiratory responses to bronchoconstriction in asthma have been partially assessed and their significance is unclear. In 44 mild asthma patients we investigated respiratory responses during increasing levels of methacholine-induced bronchoconstriction. Inspiratory muscle activity, tidal volume, inspiratory and expiratory times were continuously monitored; breathing discomfort was rated.

Summary of papers presented at the 2012 seventh international cough symposium.

Twenty six papers were presented as posters in the Seventh International Symposium on Cough; 12 papers were presented in the Basic Science of Cough session, and 14 papers presented in the Clinical Science of Cough session. These papers explored a wide spectrum of cough-related areas including pathophysiological mechanisms, treatment and detection of cough, and symptom assessment and perception, and were grouped into several general themes for facilitate the discussion. Studies presented in these posters have provided new information that should improve our knowledge on the basic physiology and pharmacology of cough, and the peripheral and central neural mechanisms involved in the generation of the cough motor pattern.

Voluntary and reflex cough: similarities and differences.

Cough is defensive airway reflex subjected to a high degree of cortical control. Not surprisingly, all cough motor patterns can be mimicked and reflex cough be inhibited up to complete suppression, at least to a certain extent. Reflex cough differentiates from other airway reflex responses for its characteristic 3-phase motor pattern, and such pattern is maintained when coughing is produced voluntarily.

Respiratory expulsive efforts evoked by maximal lung emptying.

Background: Some patients exhibit cough-like expiratory efforts ("deflation cough") during slow vital capacity (SVC) and/or FVC maneuver. The cause and motor features of these expulsive efforts are unknown.

Methods: Of 1,720 consecutive patients, 43 displayed deflation cough during SVC or FVC, and 18 agreed to participate in additional examinations involving radiologic and clinical assessments.

Desensitization of the cough reflex by exercise and voluntary isocapnic hyperpnea.

Little is known about the effects of exercise on the sensory and cognitive aspects of coughing evoked by inhalation of tussigenic agents. The threshold for the cough reflex induced by inhalation of increasing nebulizer outputs of ultrasonically nebulized distilled water (fog), an index of cough reflex sensitivity, was assessed in twelve healthy humans in control conditions, during exercise and during voluntary isocapnic hyperpnea (VIH) at the same ventilatory level as the exercise. The intensity of the urge to cough (UTC), a cognitive component of coughing, was recorded throughout the trials on a linear scale.

Downregulation of cough by exercise and voluntary hyperpnea.

No information exists on the effects of hyperpnea on the sensory and cognitive aspects of coughing evoked by inhalation of tussigenic agents. The threshold for the cough reflex induced by inhalation of increasing concentrations of ultrasonically nebulized distilled water (fog), and the index of cough reflex sensitivity, was assessed in 12 healthy humans in control conditions, during exercise, and during voluntary isocapnic hyperventilation (VIH) to the same level as the exercise. The intensity of the urge-to-cough (UTC), a cognitive component of coughing, was also recorded throughout the trials.

Targeting drugs to the airways: The role of spacer devices.

Aim: Spacer devices are inhalation aids of varying dimension and complexity, specifically designed to overcome problems with the use of pressurised metered dose inhalers (pMDIs). The aim of this review is to examine the current understanding about these inhalation devices and discuss their advantages and disadvantages.

Methods: The pertinent literature concerning the characteristics and effects of spacers on delivery and lung deposition of inhaled medications, as well as their clinical efficacy in patients with reversible airway obstruction, is examined.

Poster discussion: summary. Fifth International Cough Symposium.

At the Fifth International Cough Symposium 16 posters were presented and, as well as discussions at the poster sites, were considered in a formal symposium session. Here they are divided into groups and we summarize the discussions.

Cough reflex responses during pulmonary C-fibre receptor activation in anesthetized rabbits.

We investigated the changes induced by pulmonary C-fibre receptor activation in the cough reflex evoked by mechanical stimulation of the tracheobronchial tree in pentobarbitone anesthetized, spontaneously breathing rabbits. Phrenic nerve and abdominal muscle activities were monitored along with tracheal and arterial blood pressures. The activation of pulmonary C-fibre receptors by means of right atrial injection of phenylbiguanide (PBG) caused the pulmonary chemoreflex characterized by tachypnea, bradycardia and hypotension.

Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit.

We have previously shown that ionotropic glutamate receptors in the caudal portion of the nucleus tractus solitarii (NTS), especially in the commissural NTS, play a prominent role in the mediation of tracheobronchial cough and that substance P potentiates this reflex. This NTS region could be a site of action of some centrally acting antitussive agents and a component of a drug-sensitive gating mechanism of cough. To address these issues, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30-50 nl) of centrally acting antitussive drugs into the caudal NTS of pentobarbitone-anesthetized, spontaneously breathing rabbits.

Agreement between two methods for assessing bioequivalence of inhaled salbutamol.

For inhaled medications, bioequivalence testing is becoming increasingly important owing to the availability of many inhalation devices. We evaluated agreement between the Finney bioassay and the Emax model in the assessment of bioequivalence of salbutamol administered via a metered-dose inhaler with a spacer (pMDI+ Volumatic) or via a dry-powder inhaler (Diskus) in asthmatic patients with methacholine-induced bronchoconstriction. Eighteen patients inhaled methacholine until FEV 1 decreased by approximately 35% of control.

Before we get started: what is a cough?

Cough is an airway defensive reflex consisting of an inspiratory phase followed by a forced expiratory effort initially against a closed glottis, followed by active glottal opening and rapid expiratory flow. The expiration reflex (ER) differentiates from cough for the lack of a preparatory inspiration. The reflexes subserve different functions: cough will clear the lower airways from debris and mucus, while the expiration reflex will prevent aspiration.