HMGB1 in nasal inflammatory diseases: a reappraisal 30 years after its discovery.

INTRODUCTION: High mobility group protein box 1 (HMGB1) is a protein belonging to the alarmin family. HMGB1 has a relevant role in starting the inflammatory cascade by means of receptors, such as RAGE and TLR. HMGB1 supports transcription of many genes in interactions with many transcription factors, including NF-kB. The axis HMGB1-RAGE-NF-kB has, therefore, a pivotal role in the inflammatory cascade. HMGB1 controls the production of several pro-inflammatory cytokines and the proliferation and activation of many inflammatory cells. AREAS COVERED: The present report concerns the role of HMGB1 in nasal inflammatory disorders, including allergic and non-allergic rhinitis, and chronic rhinosinusitis with nasal polyps. HMGB1 modulation has been the aim of several studies. The literature search included recent papers that covered this topic. EXPERT OPINION: As HMGB1 has a pivotal role in inflammatory events, its modulation could be attractive for designing new therapeutic strategies. In this regard, glycyrrhetic acid (GA), the active component of Glycyrrhiza glabra, can efficiently block HMGB1. Promising reports seem to suggest that GA could exert favorable anti-inflammatory activity in patients with nasal inflammatory disorders.

New case of concha bullosa from Bronze Age Iberia (Granada, Spain).

OBJECTIVE: This study aims to expand knowledge of Concha bullosa in a prehistoric population. MATERIALS: The skull of an adult female from the Bronze Age archeological site ofCastellón Alto (Granada, Spain), dated between 1900 and 1600 BCE. METHODS: The diagnosis of middle turbinateconcha bullosa was based on macroscopic, radiographic, and computed tomography studies. RESULTS: This is one of the oldest findings ofconcha bullosa in Europe. Despite the possible obstruction of the osteomeatal complex by the concha bullosa in this individual, no signs of sinusitis were observed in maxillary sinuses. CONCLUSIONS: The maxillary sinuses of this female showed no signs of sinusitis related to theconcha bullosa. SIGNIFICANCE: This study provides new evidence on the chronological limits of this condition. The particular funeral rites of these populations have preserved the majority of skeletons at this site in an excellent condition. LIMITATIONS: The identification ofconcha bullosa continues to be rare in ancient populations, in part due to the poor preservation of nasal bones in archeological collections. Suggestions for further research: Detailed study of the nasal cavity of adequately preserved individuals can be expected to identify further cases of concha bullosa in ancient populations.

Is there a relationship between sinusitis and psychological disorders?

Chronic rhinosinusitis refers to inflammation of the nasal and sinuses mucosa and the main criteria for diagnosis of this disease related to the nasal cavity or the facial area. According to several reports based on the relationship of this disease with mental disorders, psychological issues are missing in the criteria of chronic rhinosinusitis diagnosis. In this study the etiology and clinical symptoms of the disease were studied by searching scientific databases and authentic Iranian Medicine books such as Avicenna's book The Canon of Medicine (Al-Qanun fi't-Tibb) that now taught in medicine schools of the Traditional East Asian; the results of this study showed that rhinosinusitis accompaniment with psychological symptoms are listed in abundance not only in old books but also in scientific literature before 1928 but after the discovery of antibiotics and extreme attention in the context of physiopathological assignment of diseases to pathogens, this relationship has been weakened. Given the positive results of recent studies on rhinosinusitis accompaniment with psychological disorders it is suggested that more studies are needed to explore the relationship between chronic rhinosinusitis and psychological diseases and, if necessary, to be included in the diagnostic criteria as a diagnostic standard.

Past, present and future of macrolide therapy for chronic rhinosinusitis in Japan.

In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

Sinusitis in people living in the medieval ages.

Breathing vitally serves body homeostasis. The prevalence of upper airway infections is often taken as an indicator of overall health status of a population living at a given time. In the present study we examined the unearthed remains of skulls from the XIII-XV century inhabitants searching for signs of maxillary sinusitis. Maxillary sinuses of the skulls of 92 individuals were inspected macroscopically and, if necessary, endoscopically. Osseous changes, including the pitting and abnormal spicule formation were present in 69 cases (75.0 %). It was found that, overall, dental infection was a major cause of maxillary sinusitis (18.8 %). Severe bone changes were observed in the adults' skulls, but were also present in the sinus walls of children's skulls. Post-inflammatory changes were manifest as remodeling and damage to the sinus walls. The results indicate that both children and adults of the Middle Ages suffered from chronic sinusitis. These observations confirm that the climate, environment, and lifestyle of the medieval populations contributed to the morbidity of the upper respiratory tract.

[Sinobronchitis--historical aspect]. / Zespól zatokowo-oskrzelowy w aspekcie historycznym.

There is evidence that a link exists between the upper and lower respiratory tracts. During the last fifty years many clinical observations has lead to a new pathogenic view of rhinosinusitis and asthma defined as Sinobronchial Syndrome. The inflammatory process in the nose and bronchi explains some of the complex interactions among different clinical diseases, such as rhinosinusitis, asthma, bronchial hyperresponsiveness and viral infections.

Postnasal drip syndrome. Two hundred years of controversy between UK and USA.

This review discusses the trans-Atlantic controversy concerning Post Nasal Drip Syndrome (PNDS). PNDS was described as a common condition in the UK in the nineteenth century and was so extraordinarily prevalent in the USA that it was called 'American catarrh'. American chest physicians adopted PNDS as the most common cause of chronic cough. A relationship between PNDS and chronic cough was not accepted by UK chest physicians, who preferred to use the term 'rhinosinusitis' instead of PNDS. In the USA the diagnosis of PNDS was linked to a response to therapy with a sedating antihistamine and decongestant, but UK physicians doubted if this was a specific therapy and did not accept the therapy as diagnostic for PNDS. In 2006 the American College of Chest Physicians replaced the term PNDS with upper airway cough syndrome and some UK otolaryngologists proposed that PNDS should be replaced with rhinosinusitis. PNDS is now being replaced with more general descriptions of upper airway disease and a causal link with chronic cough is now disputed. PNDS may be caused by a mucus hypersecretory phenotype that develops following chronic exposure of the respiratory tract to particulate matter, allergens, irritants and pathogens. Current research on treating excessive airway mucus in the lower airways may be applicable to PNDS.

[A medical history of Bernardo O'Higgins (1778-1842)]. / Historial médico de Bernardo O'Higgins Riquelme (1778-1842).

Bernardo O'Higgins was a very apprehensive individual regarding his health and ailments. This fact is clearly reflected in his letters, that provide valuable anamnestic data. During his youth, while living is Spain, he suffered of yellow fever and later in Chile, he probably had an acute phase of a rheumatic fever. Since his adolescence, he was affected by a chronic hlepharo-conjunctivitis. During the Chilean independence revolution, he suffered several battle wounds. The most severe was a shot that affected both his right arm and elbow (1818). While living in Peru (1823-1842) he suffered of dysentery and malaria. The latter was an endemic disease in the valleys of Peru. Being previously asymptomatic, he started experiencing extensional dyspnea, angor pectoris and syncopal episodes in 1840. At that time, physicians diagnosed a hypertrophic cardiomyopathy. Analyzing his symptoms and taking into account their short term evolution, the author concludes that they were a consequence of either an aortic stenosis or coronary insufficiency. These led him to a heart failure that was his immediate cause of death in 1842.

[The thesis of Reininger (1722) in the history of pituitary sinuses]. / La thèse de Reininger (1722) dans l'histoire des sinus pituitaires.

The thesis written by Sebastian Reininger in 1722 was conserved by Albert de Haller, the renowned scholar who collected interesting medical publications in the 18th century. He included Reininger's work on the pituitary sinuses in his Disputationes anatomicae. This thesis is probably the first published work dealing exclusively with the sinuses and their anatomy, function and pathology. There are also some comments on therapy. It was thus written before thesis by Ludolph Heinrich Runge (1750) often cited as the earliest work in this field. The Reininger dissertation is based on a personal series of cranial dissections and is completed with references to other authors of the same period. It is an interesting synopsis of the knowledge of pituitary sinuses at the beginning of the 18th century.

Patrick Watson-Williams and the concept of focal sepsis in the sinuses: an historical caveat for functional endoscopic sinus surgery.

From 1900 to 1940 the theory of focal sepsis was invoked to justify a number of dubious surgical procedures. Surgeons believed they were acting rationally. Patrick Watson-Williams advocated suction exploration of the paranasal sinuses for mental patients, claiming to cure criminal insanity by sphenoidotomy. Favourable contemporary reviews showed international approval. The rational basis of treatment was emphasised, but there was little systematic evaluation of outcome. Current enthusiasm for functional endoscopic sinus surgery is also based on a rational approach, logical deductions from pathophysiological 'facts'. Outcome has still not been evaluated scientifically. We should learn from history. Treatment should not be based too readily on what seems to be rational now. Ideas of physiology and pathology change. What seems logical today may appear ridiculous tomorrow. Careful analysis of outcome, preferably by controlled clinical trials, is needed as a rational treatment requires empirical validation just as much as any other.