Current Respiratory Medicine Reviews - Volume 9, Issue 1, 2013

Pulmonary function tests are commonly used within research to characterize disease patterns of obstructive airway diseases, and to describe lung growth and development. 20 out of 52 European birth cohorts within the ENRIECOand GA2LEN-networks reported a total of 80 investigation time-points using pulmonary function assessments. Information on published results and guidelines used were complemented through publicly available data and peer reviewed journals. Only 4 cohorts used the same test for at least 3 time-points during their follow-up. The tests were used to classify airway obstruction, bronchodilator response and bronchial hyperresponsiveness. Related methods assessed airway inflammation non-invasively. International guidelines, used in clinical practice, (American Thoracic Society/ European Respiratory Society) should be considered and referred to whenever possible to improve comparability. A consensus on when and how pulmonary function tests are beneficial in population based research, assessing lung growth or asthma subtypes, is needed.

With improving awareness, diagnostic techniques and evolving therapeutic strategies, large airway pathology is becoming an increasing, complex and challenging problem for physicians involved in the management of patients with diverse benign and malignant disease. Endobronchial intervention using rigid bronchoscopy has an established role in managing many large airway pathologies e.g. malignant conditions and for other benign diseases it is being developed. Successful outcome depends not only on familiarity with the techniques available but also on a cohesive multidisciplinary team working together with input from doctors skilled in the art of rigid and flexible bronchoscopy, anaesthetists, nurses, theatre recovery staff, operating department assistants and practitioners.

In this review we have summarized the known virulent factors of P. aeruginosa in the development of ventilator associated pneumonia (VAP). This gram negative rod bacterium colonizes through several pathogenic mechanisms that can be summarized as follows: 1) cell surface virulence factors; 2) secreted virulence factors; 3) type secretion system; 4) quorum sensing. Another additional aspect that is covered is the capacity of P. aeruginosa of organized growth as a biofilm, which is a particular growth pattern in which bacteria gain high levels of antimicrobial resistance. The development of new antimicrobial strategies may use this understanding of the bacterium behavior for possible prevention, or eradication of the infective agent, in case of severe infections.

Fibrocytes were initially described in 1999 and since that time there has been a growing body of literature to suggest their importance in a number of chronic lung diseases. It is now well established that fibrocytes derive from the bone marrow and circulate within the peripheral blood. However, when injury occurs, fibrocytes can travel to the site of damage via chemokine-mediated recruitment. Recent studies suggest that fibrocyte numbers increase within the lung or circulation during numerous disease processes. Although fibrocytes readily differentiate into fibroblasts in vitro, whether they do so readily in vivo is still unclear. Additionally, while human studies often show evidence of α-smooth muscle actin (SMA) expression in fibrocytes, this is less common in murine studies. A variety of pro-fibrotic mediators that are secreted by fibrocytes make it likely that they can act via paracrine functions to influence the behavior of resident lung cells. This review summarizes recent insights regarding fibrocytes in asthma, scleroderma and IPF.

Asthma is a prevalent and sometimes debilitating lung disorder caused by diverse triggers in susceptible individuals. Based on the salutary effect of drugs relaxing airway smooth muscle (ASM) in the treatment of asthma, there is no doubt that airway narrowing elicited by ASM shortening is involved in the development of symptoms. Asthmatic individuals are also commonly hyperresponsive to stimuli acting directly on ASM, such as methacholine; especially when they are not treated optimally. This feature is called airway hypperresponsiveness (AHR) and is thought to contribute importantly to asthma symptoms. This is because the airway response measured in an experimental setting, such as during a methacholine challenge, is a good surrogate of the airway response that would occur in vivo in response to contractile agonists generated endogenously (e.g., leukotriene and histamine) following exposure to asthma triggers. Many muscle and non-muscle factors, as well as their interaction, can contribute to AHR. The present review focuses exclusively on muscle factors. It is important to understand that many contractile properties of ASM may allow narrowing of airways in vivo. These include force, amount and velocity of shortening, stiffness, ability to relax, and ability to tolerate and recover from oscillating stress caused by breathing maneuvers. It is also important to understand that the contractile capacity of ASM can vary in time and in response to external cues (ASM is adaptable). Any permanent and transient defect in any ASM contractile property can be linked to the manifestation of AHR. Evidence supporting these links in asthma is growing.

Abnormal antenatal lung growth can result in a high mortality and morbidity, thus accurate diagnosis and effective preventative measures are essential. We have critically reviewed the literature to identify whether current diagnostic tools yield results predictive of outcome and whether antenatal interventions do prevent abnormal lung growth. Three-dimensional (3D) ultrasound examination provides more accurate information than 2D ultrasound on fetal lung volume prior to 34 weeks of gestation, but can be inaccurate if there is oligohydramnios. In addition, fetal lung volumes obtained by 3D ultrasound analysed by Virtual Organ Computer Aided analysis (VOCAL) can predict neonatal respiratory outcomes. Fetal lung volume assessments by magnetic resonance imaging (MRI) correlate with lung to head ratio results obtained by 2D ultrasound results, with an observed/expected ratio of 0.25 predicting poor survival. MRI using quantitative signal analysis gives a functional assessment of the lung parenchyma. MRI, however, is expensive and has limited patient acceptability. Antenatal interventions attempting to prevent pulmonary hypoplasia include amnioinfusion which can relieve oligohydramnios in preterm, premature rupture of the membranes, but there are insufficient data on longer term outcomes to recommend it for routine practice. In severe idiopathic oligohydramnios, amnio-infusion might prolong the duration of the pregnancy, but there is no evidence to date that it improves neonatal mortality. Thoracoamniotic shunting results in effective drainage of pleural effusions facilitating resuscitation, but it is usually performed too late in pregnancy to influence lung growth and there are complications. Pleural effusions can also be managed by pleurodesis using either OK-432 or autologous blood. In fetuses with a congenital diaphragmatic hernia (CDH) obstruction of the normal egress of fetal lung fluid by placing a balloon in the trachea (fetal tracheal obstruction (FETO)) in non randomized studies, appear to improve survival. The results of randomised trials of FETO with long term outcomes are eagerly awaited.