The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Members of the Fleischner Society compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984 and 1996 for thoracic radiography and computed tomography (CT), respectively. The need to update the previous versions came from the recognition that new words have emerged, others have become obsolete, and the meaning of some terms has changed. Brief descriptions of some diseases are included, and pictorial examples (chest radiographs and CT scans) are provided for the majority of terms.

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Fleischner Society: Glossary of Terms for Thoracic Imaging

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

/pdf/european-position-paper-on-rhinosinusitis-and-nasal-polyps-mj734vsl7p.pdf

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

/pdf/international-ers-ats-guidelines-on-definition-evaluation-sedelwbk4v.pdf

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/- 0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/- 9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.

Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease.

Primary ciliary dyskinesia (PCD) is characterized by disease of the upper and lower respiratory tract, in association with visceral mirror image arrangement in 50% of cases, due to abnormal structure and/or function of cilia. The purpose of this paper is to review the clinical features, diagnosis and management of PCD. Presentations include neonatal respiratory distress, recurrent lower respiratory tract infection, chronic rhinosinusitis and male infertility. PCD enters the differential diagnosis of bronchiectasis, atypical asthma, and unusually severe upper airway disease. Diagnosis is by a cascade of investigations, starting with the saccharin test in patients older than 10 yrs; ciliary beat frequency and pattern on light microscopy; and electron microscopy to assess ciliary morphology and orientation. It is important not to confuse primary and secondary ciliary abnormalities. Nasal nitric oxide is low in PCD, and this measurement shows promise as a screening test for PCD. Diagnosis is important, in order to prevent the development of bronchiectasis and to avoid any unnecessary otorhinolaryngological procedures. Regular follow-up is essential, and management should be multidisciplinary, with input from centres with a special interest in PCD, having access to paediatric and adult chest physicians, otolaryngologists and audiological physicians, physiotherapists, counselling services and fertility clinics. The prognosis is good, but morbidity can be considerable if PCD is incorrectly managed.

https://erj.ersjournals.com/content/erj/12/4/982.full.pdf

Primary ciliary dyskinesia: diagnosis and standards of care

There is no disease-specific instrument available for health status assessment in bronchiectasis. We examined the stability, validity and responsiveness of a measure designed for asthma and COPD, the St. George's Respiratory Questionnaire (SGRQ), in this condition. One hundred and eleven patients were studied on 2 separate d 6 mo apart. On both days each patient completed the SGRQ and measures of general and disease-specific health, mood, and fatigue. They also performed a shuttle walking test and comprehensive lung function tests. Repeatability was tested over 2 wk in 23 patients. The intraclass correlation (ri) for the SGRQ Total score was 0.97. The SGRQ component scores correlated well with relevant markers of disease activity. Examples include: SGRQ Symptoms score versus MRC Wheeze score, r = 0.634, p < 0.0001; Activity score versus shuttle walking test, r = -0.659, p < 0.0001; and impacts score versus physical fatigue, r = 0.610, p < 0.0001. Changes in the SGRQ Total score from entry to follow-up also correlated with changes in other measures of the patients' health. There were significant differences in the SGRQ total score between patients who improved and those who deteriorated over the 6 mo in respect to wheeze (F = 5.6, p < 0.01) and breathlessness (F = 6.05, p < 0.01). We conclude that the SGRQ reflects impaired health in bronchiectasis patients.

Validation of the St. George's Respiratory Questionnaire in bronchiectasis.

Bronchiectasis is characterized by chronic inflammation in one or more bronchi, but the extent of inflammation is difficult to monitor. The concentration of nitric oxide (NO) in exhaled air is increased in asthmatic patients, possibly as a result of the chronic inflammatory process. We have measured exhaled NO in patients with documented bronchiectasis and investigated whether the concentration of exhaled NO is related to the extent of disease as defined by computed tomography (CT) and lung function. In 20 patients with bronchiectasis who were not taking inhaled steroids, the peak concentration of NO in exhaled air, measured by a modified chemiluminescence analyzer, was significantly elevated (285 +/- 49.0 ppb) as compared with values for 79 normal subjects (89 +/- 2.7 ppb, p < 0.01) and 19 patients with bronchiectasis treated with inhaled steroids (88 +/- 13.4 ppb, p < 0.01). Thin-section CT was used to quantify the extent of bronchiectasis in the 19 patients. There was a significant correlation between the CT score and FEV1 (r = 0.73, p < 0.01). In patients not treated with inhaled steroids there was a significant relationship between CT score and peak exhaled NO (r = 0.81, n = 12, p < 0.02), but this was not the case for patients treated with regular inhaled steroids (n = 7). We conclude that untreated bronchiectasis is associated with an increase in exhaled NO, and that this is correlated with disease severity, whereas patients treated with inhaled steroids have levels of exhaled NO within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated levels of exhaled nitric oxide in bronchiectasis.

It has been suggested that proteinase enzymes could play an important role in the pathogenesis of chronic bronchial infections including bronchiectasis and cystic fibrosis (CF). Because Pseudomonas aeruginosa frequently colonizes the respiratory tract in bronchiectasis and CF, we examined the in vitro effects of human neutrophil elastase (HNE) and proteinase enzymes produced by P. aeruginosa (elastase: PE; alkaline proteinase: PAP) on the ciliary beat frequency (CBF) and ultrastructure of human nasal ciliated respiratory epithelium. HNE (500 micrograms/ml) progressively reduced CBF and caused marked epithelial disruption; lower concentrations (100 and 20 micrograms/ml) also caused epithelial disruption but without slowing CBF. The effects of HNE (500 micrograms/ml) were completely abolished by adding alpha 1-antitrypsin (5 mg/ml). There was no synergy between HNE and pyocyanin, a product of P. aeruginosa which slows CBF. PE in phosphate-buffered saline also caused epithelial disruption without slowing CBF; however, PE in medium containing divalent metal ions caused CBF slowing as well as epithelial disruption at 100 micrograms/ml. PAP (500 micrograms/ml) had almost no effect on ciliated epithelium. The effects of HNE and PE on nasal and bronchial epithelium obtained from the same patient were similar. Light and transmission electron microscopy revealed that HNE and PE were cytotoxic and caused detachment of epithelial cells from neighboring cells and the basement membrane. There was cytoplasmic blebbing of the cell surface and mitochondrial damage; however, no increase of abnormalities in the ultrastructure of cilia on living cells was seen. These results support the hypothesis that HNE and PE contribute to the delayed mucociliary clearance and epithelial damage that is observed in patients with chronic bronchial infection.

Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium.

AIM: To examine strains of Pseudomonas aeruginosa for specific antifungal factors. METHODS: Two clinical strains of P aeruginosa with strong in vitro inhibition (by cross streak assay) of Candida albicans and Aspergillus fumigatus were examined. Both strains were isolated from sputum--one from a patient with cystic fibrosis and one from a patient with bronchiectasis. Bacterial extracts were fractionated by high performance liquid chromatography and examined by ultraviolet absorbance and mass spectroscopy. Antifungal activity against C albicans and A fumigatus was determined in a well plate assay. RESULTS: Pyocyanin was the major antifungal agent of P aeruginosa; 1-hydroxy-phenazine also possessed activity. Pyocyanin MICs for C albicans and A fumigatus were > 64 micrograms/ml. These phenazines were active against nine other yeast species pathogenic for man. Preliminary experiments also suggested possible inhibition of yeast mycelial transformation in C albicans by pyocyanin. CONCLUSIONS: There may be a role for pyocyanin and 1-hydroxyphenazine in the prevention of pulmonary candidiasis in patients colonised by P aeruginosa.

https://jcp.bmj.com/content/jclinpath/52/5/385.full.pdf

Peter J. Cole

Papers

Primary ciliary dyskinesia: diagnosis and standards of care

Validation of the St. George's Respiratory Questionnaire in bronchiectasis.

Elevated levels of exhaled nitric oxide in bronchiectasis.

Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium.

Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth.