Academic literature on the topic 'Chronic respiratory infection'

The breadth and quality of scientific presentations on clinical and translational research into respiratory infections at the 2015 European Respiratory Society (ERS) International Congress in Amsterdam, the Netherlands, establishes this area as one of the leadings fields in pulmonology. The host–pathogen relationship in chronic obstructive pulmonary disease, and the impact of comorbidities and chronic treatment on clinical outcomes in patients with pneumonia were studied. Various communications were dedicated to bronchiectasis and, in particular, to different prognostic and clinical aspects of this disease, including chronic infection with Pseudomonas and inhaled antibiotic therapy. Recent data from the World Health Organization showed that Europe has the highest number of multidrug-resistant tuberculosis cases and the poorest countries have the least access to suitable treatments. Latent tuberculosis and different screening programmes were also discussed with particular attention to risk factors such as HIV infection and diabetes. Several biomarkers were proposed to distinguish between active tuberculosis and latent infection. Major treatment trials were discussed (REMOX, RIFQUIN and STREAM). The possibility of once-weekly treatment in the continuation phase (RIAQUIN) was especially exciting. The continuing rise of Mycobacterium abscessus as a significant pathogen was noted. This article reviews some of the best contributions from the Respiratory Infections Assembly to the 2015 ERS International Congress.

AbstractThe relationship between upper and lower respiratory tract infections has been demonstrated previously, although the effect of chronic infection of One tract on the other has not been well studied. This work analyses the broncho-alveolar lavage fluid of patients with chronic purulent rhino-sinusitis and reveals and increase in the neutrophil nitro-blue tetrazolium dye reduction test positivity provides evidence for increased phagocutosis to compensate for the increased contamination of the lower respiratory tract.

IntroductionNon-cystic fibrosis (CF) bronchiectasis (“bronchiectasis”) is a chronic airway disease for which little data exist to inform treatment decisions. We sought to compare the risks of respiratory infections in chronic users of inhaled corticosteroids (ICSs) versus macrolide monotherapy.MethodsWe identified a cohort of US Medicare enrollees with a bronchiectasis diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 494.0 or 494.1) between 2006 and 2014, excluding CF. We defined chronic new use as the first ≥28-day prescription of ICS therapy or macrolide monotherapy. We compared the characteristics of the exposure cohorts using standardised mean differences (SMDs) and computed a propensity score (PS) to account for treatment differences. The risks of acute exacerbation, hospitalised respiratory infection, all-cause hospitalisation and mortality were compared using PS decile-adjusted Cox regression models.ResultsWe identified 83 589 new users of ICSs and 6500 new users of macrolides from 285 043 included Medicare enrollees with bronchiectasis. The crude incidence of hospitalised respiratory infection was 12.6 (ICS therapy) and 10.3 (macrolide monotherapy) per 100 patient-years. The PS-adjusted HRs comparing ICS with macrolide new users were 1.39 (95% CI 1.23–1.57) for hospitalised respiratory infection, 1.56 (95% 1.49–1.64) for acute exacerbation and 1.09 (95% 0.95–1.25) for mortality.InterpretationAmong patients with bronchiectasis, the use of ICSs was associated with an increased risk of hospitalised respiratory infections compared with macrolide monotherapy.

Pseudomonas aeruginosa (P. aeruginosa) is a frequently isolated pathogen that causes septicaemia and chronic respiratory infection. It exhibits a higher mortality rate than other gram-negative bacteria and the need for effective immunotherapy is emphasised by the frequency of antibiotic resistance associated with this organism. Mucosal immunisation with a whole killed cell P. aeruginosa vaccine has previously demonstrated a significant immune response in both rodent studies and human trials. This study is a continuation of that research, with the major goal being the identification of a purified protein antigen that could form the basis of a mucosal vaccine against P. aeruginosa. Specifically, the aims of this study were the development of purification protocols for the isolation of previously untested protein antigens, assessment of the efficacy of these antigens to enhance bacterial clearance in an animal model of acute respiratory infection, determination of the immune parameters that are associated with the resolution of P. aeruginosa respiratory infection and finally, cloning of an identified antigen which demonstrated vaccine efficacy. Protocols were established to isolate proteins for use as antigens in immune response studies. The proteins purified in this study were Pa 13, Azurin, acyl carrier protein (ACP), Amidase, Aminopeptidase, KatA and Pa70. These proteins were used to immunise rats by intestinal intra-Peyer's patch (IPP) inoculation and intratracheal (IT) boost. The immunisation protocol employed was designed to target mucosal antigen-specific immune responses where the route of immunisation, Peyer's patch (PP) intestinal inoculation, is akin to the oral delivery of antigens to the gut-associated lymphoid tissue (96). Investigations of a previously uncharacterised antigen, Pa60, later identified this protein as the P. aeruginosa catalase, KatA. This study demonstrated enhanced bacterial clearance of both homologous and heterologous challenge following immunisation with KatA. The level of clearance demonstrated by KatA was promising when compared to that of killed whole cell immunisation. KatA was cloned and studies with the recombinant protein showed enhanced bacterial clearance commensurate with that of the native protein. Immunisations with other proteins identified four additional antigens which enhanced bacterial clearance; Pa13, Pa40, Pa45 and Pa70. Amino acid sequence analysis indicated that Pa13 may be a novel protein, whereas Pa40 was determined to be amidase and Pa45, aminopeptidase. Pa70 was not successfully sequenced. These proteins were effective in significantly enhancing bacterial clearance of homologous P. aeruginosa challenge. For KatA, Pa13 and Pa70, clearance was associated with a marked phagocytic cell recruitment. In contrast, amidase and aminopeptidase demonstrated clearance with a minimal cellular response. Proteins; azurin and ACP were non-protective, failing to clear a live P aeruginosa challenge. Analysis of the antigen-specific responses of these nonprotective proteins and comparison with those antigens which enhanced bacterial clearance were used to determine factors that may contribute to the resolution of an acute pulmonary infection. The study has demonstrated that mucosal immunisation using purified protein antigens can enhance the clearance of pulmonary infection with P. aeruginosa. It has also contributed to the understanding of immune responses to newfound antigens of P. aeruginosa and identified antigen-specific responses which confirm their potential as vaccine candidates.

[eng] Chronic respiratory infection (CRI) by Pseudomonas aeruginosa is the main cause of morbidity and mortality in cystic fibrosis (CF). During the progression from early infection to chronic non-eradicable colonization P. aeruginosa undergoes a complex evolutionary adaptation and diversification process which eventually leads to a mixed and persistent infecting population in which multidrug resistant variants frequently rise compromising the selection of appropriate antibiotic therapies. In this work the interplay between three key microbiological aspects of these infections was investigated: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators) and the evolution of resistance to antibiotics. Clonal epidemiology, antibiotic susceptibility profiles, contribution of P. aeruginosa classical resistance mechanisms and the role of mutator variants were investigated in two large collections of CF P. aeruginosa isolates from the Balearic Islands and Spain. As well, whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, within-host evolution, WGS mutator genotypes (mutome) and resistome of widespread P. aeruginosa clonal complex 274 (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. Finally, due to the Chronic respiratory infection (CRI) by Pseudomonas aeruginosa is the main cause of morbidity and mortality in cystic fibrosis (CF). During the progression from early infection to chronic non-eradicable colonization P. aeruginosa undergoes a complex evolutionary adaptation and diversification process which eventually leads to a mixed and persistent infecting population in which multidrug resistant variants frequently rise compromising the selection of appropriate antibiotic therapies. In this work the interplay between three key microbiological aspects of these infections was investigated: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators) and the evolution of resistance to antibiotics. Clonal epidemiology, antibiotic susceptibility profiles, contribution of P. aeruginosa classical resistance mechanisms and the role of mutator variants were investigated in two large collections of CF P. aeruginosa isolates from the Balearic Islands and Spain. As well, whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, within-host evolution, WGS mutator genotypes (mutome) and resistome of widespread P. aeruginosa clonal complex 274 (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. Finally, due to the relevance of aminoglycosides in the management of CF-CRI, the dynamics of P. aeruginosa resistance development to aminoglycosides was also studied in vitro by WGS approaches. Despite discrepancies between molecular genotyping methods, a high degree of genetic diversity was documented among CF isolates from the Balearic Islands and Spain with scarce representation of CF epidemic strains. However, for the first time in Spain, we documented a superinfection with the multidrug resistant Liverpool Epidemic Strain (LES) in a chronically colonized patient. As well, P. aeruginosa CC274, previously detected in several CF individuals from Austria, Australia and France, was detected in 5 unrelated chronically colonized patients from the Balearic Islands and, therefore, this clone-type should be added to the growing list of CF epidemic clones. Subsequent analysis of the whole genomes sequences of P. aeruginosa isolates from the CC274 P. aeruginosa collection provides evidence of interpatient dissemination of mutator sublineages and denotes their potential for unexpected short-term sequence type (ST) evolution and antibiotic resistance spread, illustrating the complexity of P. aeruginosa population biology in CF. As well, epidemiological studies demonstrated the coexistence of two divergent lineages but without evident geographical barrier. Antibiotic resistance significantly accumulated overtime accompanied by hypersusceptibility to certain antibiotics such as aztreonam, which can be explained in terms of collateral susceptibility. Correlation between phenotypes and WGS genotypes of clonal isolates from the CC274 collection allowed us to define the mutational resistome of CF P. aeruginosa which extends beyond the classical mutational resistance mechanisms. Among the new chromosomic resistance determinants encountered, mutations within the penicillin-binding-protein 3 (PBP3), shaping up beta-lactam resistance, are noteworthy as well as mutations within the fusA1 gene, coding for elongation factor G, which along with MexXY overexpresion contribute to high-level aminoglycoside resistance. Strikingly, we encountered that MexXY overexpression is dispensable for in vitro resistance development to aminoglycosides which suggests an evolutionary advantage of its overexpression in the CF respiratory tract. Altogether this work demonstrates that clonal epidemiology and antibiotic resistance evolution in the CF setting results from the complex interplay among mutation-driven resistance mechanisms, within host diversification and interpatient transmission of epidemic strains.
[spa] La infección respiratoria crónica por P. aeruginosa es la principal causa de morbilidad y mortalidad en pacientes con fibrosis quística (FQ). Durante la progresión desde la infección temprana a la colonización crónica, P. aeruginosa experimenta un complejo proceso adaptativo y de diversificación que resulta en una población heterogénea y persistente en la que la aparición de resistencias a los antibióticos comprometen la selección de terapias apropiadas. En este trabajo se investigó la interacción entre tres aspectos microbiológicos clave de estas infecciones: la presencia de cepas transmisibles y persistentes, la aparición de variantes con tasas de mutación incrementadas y la evolución de la resistencia a los antibióticos. La epidemiología clonal, los perfiles de sensibilidad antibiótica, la contribución de los mecanismos clásicos de resistencia de P. aeruginosa y el papel de las variantes hipermutadoras se estudiaron en dos grandes colecciones de aislados procedentes de pacientes con fibrosis quística de las Islas Baleares y España. Asimismo, mediante secuenciación de genoma completo, se determinó la filogenia, diseminación interpaciente, evolución intrapaciente, genotipo hipermutador y resistoma de una colección de aislados clonales pertenecientes al complejo clonal 274 (CC274), proviniendo dichos aislados de dos países muy distantes, Australia y España, y cubriendo un período de 18 años. Finalmente, dada la relevancia de los aminoglucósidos en el manejo de estos pacientes, se estudió la dinámica del desarrollo de resistencia a aminoglucósidos in vitro mediante secuenciación de genoma completo. A pesar de encontrarse discrepancias entre los métodos de genotipado molecular, se documentó un alto grado de diversidad genética en las colecciones de las Islas Baleares y España, siendo escasa la representación de cepas epidémicas. No obstante, por primera vez en España, se documentó un caso de sobreinfección con el clon epidémico multirresistente de Liverpool. Además, en 5 pacientes de Baleares, crónicamente colonizados y sin aparente relación epidemiológica, se detectó el CC274. Puesto que este complejo clonal también ha sido detectado en pacientes de países como Austria, Australia y Francia, éste debería incluirse en la creciente lista de cepas epidémicas. El análisis posterior de las secuencias de genoma completo de los aislados del CC274 evidenció la diseminación interpaciente de un sublinaje hipermutador, denotando además el potencial de estas variantes para la inesperada evolución a corto plazo del secuenciotipo y la rápida diseminación de resistencias. Además, los estudios epidemiológicos demostraron la coexistencia de dos linajes divergentes, no evidenciándose barrera geográfica. Asimismo se documentó una tendencia generalizada a la acumulación de resistencias a los antibióticos en el tiempo, acompañada de hipersensibilidad a ciertos antibióticos como aztreonam, lo cual se puede explicar en términos de sensibilidad colateral. La correlación entre los fenotipos y genotipos determinados mediante secuenciación del genoma completo de los aislados pertenecientes al CC274 nos permitió definir el resistoma mutacional de P. aeruginosa en la FQ, el cual se extiende más allá de los mecanismos mutacionales clásicos. Entre los nuevos determinantes de resistencia cromosómica encontrados caben destacar tanto las mutaciones en la proteína fijadora de penicilina PBP3, que confieren resistencia a betalactámicos, como las mutaciones en fusA1, que codifica para el factor de elongación G, y que junto con la hiperexpresión de MexXY contribuyen a la resistencia de alto nivel a aminoglucósidos. Paradójicamente, encontramos que la hiperexpresión de MexXY es prescindible para el desarrollo de resistencia in vitro a aminoglucósidos, lo que sugiere que dicha hiperexpresión confiere una ventaja evolutiva in vivo. En conjunto, este trabajo demuestra que, en la FQ, la epidemiología clonal y la evolución de la resistencia a los antibióticos son el resultado de una compleja interacción entre los mecanismos de resistencia mutacionales, la diversificación de la población infectante y la transmisión interpaciente de cepas epidémicas.
[cat] La infecció respiratòria crònica per P. aeruginosa és la principal causa de morbiditat i mortalitat en els pacients amb fibrosi quística (FQ). Durant la progressió des de la infecció primerenca a la colonització crònica, P. aeruginosa experimenta un complexe procés adaptatiu i de diversificació que resulta en una població heterogènia i persistent en la qual l'aparició de variants resistents a múltiples antibiòtics comprometen la selecció de teràpies antibiòtiques apropiades. En aquest treball es va investigar la interacció entre tres aspectes microbiològics clau: la presència de soques transmissibles i persistents, l'aparició de variants amb taxes de mutació incrementades i l'evolució de la resistència als antibiòtics. L'epidemiologia clonal, els perfils de sensibilitat antibiòtica, la contribució dels mecanismes clàssics de resistència i el paper de les variants hipermutadores es van estudiar en dos grans col·leccions d'aïllats procedents de pacients amb FQ de les Illes Balears i Espanya. Així mateix, mitjançant seqüenciació del genoma complet, es va determinar la filogènia, disseminació interpacient, evolució intrapacient, genotip hipermutador i resistoma d'una col·lecció d'aïllats pertanyents al complexe clonal 274 (CC274), provenint de dos països molt distants, Austràlia i Espanya, i cobrint un període de 18 anys. Finalment, donada la rellevància dels aminoglicòsids en el maneig d’aquests pacients, es va estudiar la dinàmica del desenvolupament de resistència a aminoglicòsids in vitro mitjançant seqüenciació de genoma complet. Tot i trobar discrepàncies entre els mètodes de genotipat molecular, es va documentar un alt grau de diversitat genètica en les col·leccions de les Illes Balears i Espanya, sent escassa la representació de soques epidèmiques. No obstant això, per primera vegada a Espanya, es va documentar un cas de sobreinfecció amb el clon epidèmic multiresistent de Liverpool. A més, en 5 pacients de les Illes Balears, crònicament colonitzats i sense aparent relació epidemiològica, es va detectar el CC274. Ja que aquest complexe clonal també ha estat detectat en països com Àustria, Austràlia i França, aquest clon hauria d'incloure a la creixent llista de soques epidèmiques. L'anàlisi posterior de les seqüències de genoma complet dels aïllats pertanyents al CC274, va evidenciar la disseminació interpaciente d'un subllinatge hipermutador, denotant a més el potencial d'aquestes variants per a la inesperada evolució a curt termini del sequenciotip i per a la ràpida disseminació de la resistència antibiòtica. A més, els estudis epidemiològics van demostrar la coexistència de dos llinatges divergents, no existint barrera geogràfica. Així mateix es va evidenciar una tendència generalitzada a l'acumulació de resistències en el temps, acompanyada d'hipersensibilitat a certs antibiòtics com l’aztreonam, la qual cosa es pot explicar en termes de sensibilitat col·lateral. La correlació entre els fenotips i genotips determinats mitjançant seqüenciació del genoma complet dels aïllats pertanyents al CC274 ens va permetre definir el resistoma mutacional de P. aeruginosa en la FQ, el qual s'estén més enllà dels mecanismes de resistència mutacionals clàssics. Entre els nous determinants de resistència cromosòmica trobats cal destacar tant les mutacions en la proteïna fixadora de penicil·lina PBP3, que confereixen resistència a betalactàmics, així com les mutacions en fusA1, que codifica per al factor d'elongació G, i que juntament amb la hiperexpressió de MexXY contribueixen a la resistència d'alt nivell a aminoglucòsids. Paradoxalment, vam trobar a més que la hiperexpressió de MexXY és prescindible per al desenvolupament de resistència in vitro a aminoglucòsids, el que suggereix que aquesta hiperexpressió suposa un avantatge evolutiu in vivo. En conjunt, aquest treball demostra que l'epidemiologia clonal i l'evolució de la resistència als antibiòtics en el context de la FQ són el resultat d'una complexa interacció entre els mecanismes de resistència mutacionals, la diversificació de la població infectant i la transmissió interpaciente de ceps epidèmiques.

Aims To assess the impact of RSV and other viral lower respiratory tract infections (LRTIs) on chronic respiratory morbidity in prematurely born infants and to investigate whether there were any functional or genetic predisposing factors. Methods One hundred and fifty three prematurely born infants were followed until one year corrected age with approximately half followed until two years of age. Lung function was measured at 36 weeks postmenstrual age (PMA) and one year corrected age. Blood or buccal swabs were taken for single nucleotide polymorphism (SNP) analysis. Following neonatal unit discharge, a nasopharyngeal aspirate (NPA) was taken whenever an infant had a LRTI. NPAs were analysed by real time PCR for 13 viruses. At one and two years corrected age healthcare utilisation and costs of care were calculated and parents completed a respiratory health related questionnaire and a diary card for one month. Results Infants developing RSV or other viral LRTIs requiring hospitalisation had reduced premorbid lung function compared to infants not hospitalised. Infants developing rhinovirus LRTIs had increased healthcare utilisation, cost of care and wheeze at one year corrected age. Infants developing RSV LRTIs had reduced lung function at one year corrected age. Prematurity was found to be a risk factor for developing RSV or other viral LRTIs but not influenza A (H1N1) LRTIs. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36 week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (IL10, NOS2A, SFTPC, MMP16 and VDR) and reduced lung function at one year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs. Conclusion In prematurely born infants, RSV and other viral LRTIs were associated with increased chronic respiratory morbidity at follow up, with some infants being genetically predisposed to this after RSV LRTI. Premorbid abnormal lung function predisposed to severe RSV and a SNP in the ADAM33 gene predisposed to RSV LRTIs.

In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal β-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. Previous studies showed that in addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, the transcriptional profiles generated using DNA microarrays and RNA-Seq of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant, PAO∆ampR were analyzed. Transcriptome analysis demonstrates that the AmpR regulon is much more extensive than previously thought influencing the differential expression of over 500 genes. In addition to regulating resistance to β-lactam antibiotics via AmpC, AmpR also regulates non-β-lactam antibiotic resistance by modulating the MexEF-OprN efflux pump. Virulence mechanisms including biofilm formation, QS-regulated acute virulence, and diverse physiological processes such as oxidative stress response, heat-shock response and iron uptake are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the transcriptome data. Further, Caenorhabditis elegans model demonstrates that a functional AmpR is required for full pathogenicity of P. aeruginosa. AmpR, a member of the core genome, also regulates genes in the regions of genome plasticity that are acquired by horizontal gene transfer. The extensive AmpR regulon included other transcriptional regulators and sigma factors, accounting for the extensive AmpR regulon. Gene expression studies demonstrate AmpR-dependent expression of the QS master regulator LasR that controls expression of many virulence factors. Using a chromosomally tagged AmpR, ChIP-Seq studies show direct AmpR binding to the lasR promoter. The data demonstrates that AmpR functions as a global regulator in P. aeruginosa and is a positive regulator of acute virulence while negatively regulating chronic infection phenotypes. In summary, my dissertation sheds light on the complex regulatory circuit in P. aeruginosa to provide a better understanding of the bacterial response to antibiotics and how the organism coordinately regulates a myriad of virulence factors.

The aim of this research project was to determine whether temperate bacteriophages could be used as markers for bacterial evolution in chronic microbial infections and in the progression of respiratory diseases [Cystic Fibrosis (CF) and Bronchiectasis (BR)]. CF and BR have diverse clinical origins but similar pathophysiological burdens including inflammation and the production of a nutrient rich mucus. This thick, dehydrated mucus is an ideal colonisation site for opportunistic bacteria such as Pseudomonas aeruginosa (P. aeruginosa). Some strains of P. aeruginosa have been found to harbour multiple inducible temperate bacteriophages that are believed to have an effect on P. aeruginosa functionality. In order to try and answer the research question proposed, the research was split into three subgroups: (1) a cross-infection study utilising 94 clinical P. aeruginosa isolates and their associated mixed phage communities to determine changes in phage-host interactions alongside the progression of the clinical disease. We here illustrate that phages induced from the older CF patient isolates were the most infective, whilst the phages originating from the youngest CF patients or the patients with < 10 years of BR diagnosis were the least infective. (2) Metagenome analysis of the total induced viral DNA from each of these 94 P. aeruginosa isolates was used to determine whether disease progression offered complexity or additional gene function that would offer a selective advantage for the bacterium or virus in these clinical backgrounds. This research importantly shows differences in phage metagenome complexity and an increase in gene function that correlates with the advancement of disease progression. Therefore, phage metagenomes originating from the older CF patients were the most enriched in functions relating to survival within the chronic lung. It also shows a snapshot of phage evolution and their impact on the bacteria colonising the lower lung. If higher numbers of phage genes with defined function is a marker of the levels of adaptation and evolution that has occurred, then this research determines that phages isolated from CF metagenomes had undergone more rounds of evolution compared to the BR metagenomes. (3) Changes in metabolite profiles in the bacterium when infected with a single phage may further show the involvement and subversion of host cell functionality by these phages. A panel of plaque-purified phages were used to create lysogens of lab strain PAO1. Changes in the metabolite profiles between naïve and infected PAO1 were investigated throughout pellicle growth where distinct differences were seen and further show the impact of prophage formation on the core gene function of respiring bacteria. Both the E. coli metabolome database and the human metabolome database were utilised in order to identify potential metabolites that were both statistically significant and had a low CV score. We illustrate different metabolite profiles when comparing naïve bacterial strain to lysogen and thus, we establish the intricacy of how the virus subverts host cell functionality. One metabolite was observed that was present in a lysogenic strain and not in the naïve host cell, so potentially leading to the assumption that this metabolite is phage derived. Further LCMS work is required in order to confirm this preliminary finding.

Respiratory medicine is a diverse specialty involving common chronic diseases, rarer conditions, pulmonary involvement in systemic disorders, lung infections, tumours, and adverse drug effects. It is also an important component of general internal medicine. Respiratory medicine has been prominent in producing clinical guidelines, many of which are now evidence-based, and hence a good source of information and reference. Some of the commonest medical conditions, including asthma and lung cancer, are rooted in respiratory medicine. Although declining, lag effects mean these conditions are increasingly prevalent and continue to be important, particularly in the developing world. Sleep medicine is now also beginning to receive attention, and respiratory infections remain common. Respiratory research is broad-based, but the level of government and major charity funding is low. This chapter summarizes important recent clinical papers under the subheadings of asthma, chronic obstructive pulmonary disease, infection, lung cancer, and smoking, with contributions from pulmonary vascular disease and sleep.

Chapter 5 covers respiratory diseases and respiratory failure, including clinical presentations of respiratory disease, assessment of diffuse lung disease, hypoxaemia, respiratory failure, and oxygen therapy, pneumonia, mycobacterial infection, asthma, chronic obstructive pulmonary disease (COPD), lung cancer, mediastinal lesions, pneumothorax, pleural disease, asbestos-related lung disease, diffuse parenchymal (interstitial) lung disease, sarcoidosis, pulmonary hypertension, acute respiratory distress syndrome, bronchiectasis and cystic fibrosis, bronchiolitis, eosinophilic lung disease, airways obstruction, aspiration syndromes, and near-drowning, pulmonary vasculitis, the immunocompromised host, sleep apnoea, and rare pulmonary diseases.

Cystic fibrosis lung disease is characterized by chronic infection, inflammation and a progressive loss of lung function. Patients are also affected by recurrent episodes of increased respiratory symptoms, called exacerbations which have a detrimental effect on quality of life, the rate of lung function decline, and mortality. Early diagnosis and treatment is vital. Diagnosis relies on a combination of symptoms, examination findings, the results of laboratory tests, and lung function. Antibiotics are the mainstay of treatment but airway clearance, nutrition, and glucose homeostasis must also be optimized. Mild exacerbations are usually treated with oral antibiotics and more severe exacerbations with intravenous antibiotics. The choice of antibiotic is guided by the patient’s chronic pulmonary infections, the in-vitro antibiotic sensitivities, known antibiotic allergies, and the previous response to treatment. In patients with chronic Pseudomonas aeruginosa infection, antibiotic monotherapy is thought to increase the risk of resistance and treatment with 2 antibiotics is therefore suggested (usually a β‎-lactam and an aminoglycoside). Although there is a lack of evidence on the duration of treatment, most patients receive around 14 days. This can be altered according to the time taken for symptoms and lung function to return to pre-exacerbation levels. If patients are carefully selected and receive appropriate monitoring, home intravenous antibiotics can be as effective as in-patient treatment. They are also associated with decreased disruption to patients / family life, decreased risk of cross infection and decreased costs.

Viral infection includes any clinical illness caused by a pathogenic virus. Acute viral infections are amongst the most common illnesses of humans and range from minor upper respiratory tract infections to viral haemorrhagic fever. The principles in diagnosing acute viral infection are, first, recognize the syndrome, then identify key features that might suggest a specific diagnosis, and, finally, consider laboratory investigations to elucidate the specific causative agent. The host–pathogen response determines different outcomes for specific viral infections. After infection with some viruses (e.g. measles virus, rubella virus) protective immunity develops, there is no latency or chronic carriage, and reinfection is prevented. Another group of viruses, in the presence of inadequate immune response, can cause chronic infection (e.g. hepatitis B and C viruses). This chapter reviews the clinical features, diagnosis, and management of acute viral infections in immunocompetent individuals.

This chapter describes the anaesthetic management of the patient with respiratory disease. It describes the assessment of respiratory function and preoperative respiratory investigations, and ventilatory strategies to reduce pulmonary complications. Common respiratory conditions covered include respiratory tract infection, smoking, asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea, sarcoidosis, restrictive pulmonary disease, and the patient with a transplanted lung. For each topic, preoperative investigation and optimization, treatment, and anaesthetic management are described. Recommendations for the patient who may require post-operative respiratory support (e.g. non-invasive ventilation) are provided.

This chapter describes the anaesthetic management of the patient with respiratory disease. It describes the assessment of respiratory function and preoperative respiratory investigations, and ventilatory strategies to reduce pulmonary complications. Common respiratory conditions covered include respiratory tract infection, smoking, asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea, sarcoidosis, restrictive pulmonary disease, and the patient with a transplanted lung. For each topic, preoperative investigation and optimization, treatment, and anaesthetic management are described. Recommendations for the patient who may require post-operative respiratory support (e.g. non-invasive ventilation) are provided.

Includes: Aspergillus lung disease, severe asthma with fungal sensitisation, allergic bronchopulmonary aspergillosis, invasive aspergillosis, chronic pulmonary aspergillosis, summary of Aspergillus lung disease, pneumocystis pneumonia (PCP): diagnosis and treatment, cryptococcosis, candidal pneumonia, endemic mycoses, histoplasmosis, blastomycosis, endemic mycoses: coccidioidomycosis, paracoccidioidomycosis

There are unique infection prevention issues associated with pediatric long-term care facilities, behavioral health units, rehabilitation hospitals, and other residential facilities. All of these facilities provide care to children with complex, chronic medical conditions. These children are at increased risk for healthcare-associated infection due to factors such as age-related vulnerability to infections, especially respiratory viral infections; chronic exposure to indwelling medical devices such as tracheostomies, gastrostomy tubes, and central venous catheters; and frequent close contact with other children and healthcare providers during therapeutic and social activities. This chapter provides infection prevention and control guidance in special healthcare settings outside of acute care, including pediatric long-term care, behavioral health, and residential facilities. The adaptation of strategies such as transmission-based precautions while maintaining a homelike environment is described. Recommendations for infection surveillance in these setting are provided, along with algorithms for managing respiratory and gastrointestinal illness.

Measurement of physiological pressures is fundamental to many forms of medical diagnosis and monitoring in the cardiovascular, respiratory, gastrointestinal, urological and other systems. Pressure is usually measured via catheters, either connected to transducers outside the body or more recently by micro-transducers mounted on the tip of such catheters. However, this requires that the catheters be inserted and maintained without infection and that the patient be tethered to a recording device. While this may be manageable during short term tests such as urodynamics, the measurement of bladder pressure to diagnose incontinence, chronic monitoring poses an additional set of obstacles.