Asthma and chronic obstructive pulmonary disease (COPD, also called chronic airflow limitation (CAL)) are the most frequent diagnoses in patients with intrathoracic airways obstruction [1]. Often these patients show a spontaneous variability in the degree of airways obstruction, which can be documented by serial lung function measurements. Large variability in the degree of airways obstruction is indicative of an increased susceptibility of the patient to environmental stimuli that cause acute airway narrowing. Knowledge of the potential severity of these episodes of acute airways obstruction is of clinical interest. Therefore, several quantitative measures of the response of the airways to bronchoconstrictors in vivo have been advocated over the past two decades. The objective of the present guidelines is to address the methodological issues of the various available techniques, and to provide up-to-date international guidelines on standardization. The present recommendations might not represent the potentially best methodologies. However, they do represent the currently validated techniques, by which interchangeable results can be obtained among laboratories.

Variable airways obstruction can be mimicked in the laboratory by challenge tests with bronchoconstrictive stimuli (fig. 1) [2]. This enables one to measure the degree of the so-called «airway responsiveness» of the subject to a particular agent. Since the bronchoconstrictive response varies from one stimulus to another, one needs to specify the challenging agent. Therefore, the term «nonspecific» airway responsiveness should be abandoned.



Figure 1– 
Dose-response curves to inhaled methacholine using the dosimeter method in 3 subjects. Airway hyperresponsiveness in asthma is characterised by a leftward shift of the curve (hypersensitivity), a steeper slope (hyperreactivity), and an increase in maximal response (excessive airway narrowing). Modified from de Pee et al. [243] with permission.



Airway hyperresponsiveness refers to an exaggerated response to the bronchoconstrictor. This is reflected by an increased sensitivity to the stimulus, which …

https://erj.ersjournals.com/content/erj/6/Suppl_16/53.full.pdf

Airway Responsiveness. Standardized Challenge Testing With Pharmacological, Physical and Sensitizing Stimuli in Adults. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society

It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive hear...

https://www.physiology.org/doi/pdf/10.1152/physrev.00012.2007

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

THE purpose of this review is to evaluate recent developments in our understanding of the inflammatory response to cardiac surgery. Scientific knowledge in this field is continually expanding, potentially significant advances are regularly reported, and this area constitutes a major interface of clinical and basic scientific research. The review is divided into four major sections. The first section describes the pathophysiology of the inflammatory response to cardiac surgery. Factors that influence the extent of the inflammatory response, including the immunomodulatory effects of drugs commonly administered perioperatively, are discussed in the second section. The third section examines the evidence that the inflammatory response contributes to adverse perioperative events, in particular organ dysfunction, while the final section evaluates potential therapeutic strategies to control this response. The review concludes with a summary of potential future research directions and key deficiencies in our knowledge regarding the inflammatory response to cardiac surgery.

The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist.

The changes in airway occlusion pressure and airflow, occurring during two spasmodic breathing patterns, were studied and compared with normal breathing pattern in 12 anaesthetized cats. The inspiratory effort developed during the sniff-like aspiration reflex elicited by mechanical stimulation of the nasopharynx under control conditions proved to be very similar in character and intensity to the activity observed during gasping which occurred on resuscitation, of the same cats, from hypoxic apnoea. The starting (P50) and maximum (Pmax) airway occlusion pressure developed in these two spasmodic breathing patterns were very high. Extremely rapid rates of contraction and relaxation were detected by computer-assisted measurements of dynamic changes in both the pressure values and the slopes of pressure curves. The results suggest common effector mechanisms, reflecting similar forceful inspiratory drives, for the aspiration reflex and gasping. These two spasmodic processes differ substantially from normal breathing. Nevertheless, the aspiration reflex differs from gasping in that it can be elicited by activation of upper airway afferents during eupnea. Moreover, as yet, there is no definitive evidence that the brainstem mechanisms responsible for generating the aspiration reflex are the same as those of the gasp. The main benefits of this reflex are its rather easy elicitability under various conditions and its capability to induce important cardiorespiratory effects (e.g.) reversal of central apnoea) owing to its powerful activity.

https://erj.ersjournals.com/content/erj/6/1/53.full.pdf

Comparison of inspiratory effort in sniff-like aspiration reflex, gasping and normal breathing in cats

It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution.

Hypoxic pulmonary vasoconstriction.

We conducted an assessment of respiratory health status including questionnaire and spirographic measurements in 54 male swine producers age 36.3 +/- 11.1 years (mean +/- SD) who worked an average of 10.7 +/- 6.3 years in the industry and spent 4.7 +/- 2.1 hours per day in the swine barns, and we also measured atmospheric contaminants including carbon dioxide, ammonia, total dust, respirable dust, and airborne endotoxin. Mean atmospheric dust contaminant levels were as follows: carbon dioxide, 2632 +/- 807 ppm; ammonia, 11.3 +/- 4.2 ppm; total dust, 2.93 +/- 0.92 mg/m3; respirable dust, 0.13 +/- 0.05 mg/m3; and endotoxin, 11,332 +/- 13,492 endotoxin units/m3. Of these, endotoxin related to forced vital capacity (P < .05) and endotoxin x hours per day was related to forced vital capacity (P < .05) and to forced expiratory volume in 1 second (P = .06). Respiratory symptoms and lung function studies did not relate to categories of low, medium, and high exposure to respirable dust. However, categories of endotoxin (available on 46 workers) related to respiratory symptoms (cough, P = .02; chronic bronchitis, P = .06; and to forced vital capacity, P < .01). These data suggest that respiratory health status relates to endotoxin levels but not to dust level exposures in the presence of low dust levels and indicates that control measures should include endotoxin as well as dust control.

Thomas S. Hurst

Papers

Respiratory health status in swine producers relates to endotoxin exposure in the presence of low dust levels.

Respiratory Health of Swine Producers: Focus on Young Workers

Accelerated Lung Function Decline in Swine Confinement Workers

Neutrophil-mediated acute lung injury after extracorporeal perfusion

Positive Human Health Effects of Wearing a Respirator in a Swine Barn