A possible link between recurrent upper respiratory tract infections and lower cytokine production in patients with Q fever fatigue syndrome

Besides fatigue, many Q fever fatigue syndrome (QFS) patients also complain of frequently recurring upper respiratory tract infections with severe symptoms. We investigated whether immunologic dysregulation contributes to these complaints. Cytokine and chemokine production was measured after stimulating monocytes of QFS patients and age‐ and sex‐matched healthy controls with LPS and several viral ligands. The H3K4me3 mark of open chromatin was measured at the promoter regions of cytokines and chemokines that differed significantly from healthy controls. Monocytes of QFS patients produced significantly less TNF‐α (p = 0.032), IL‐1β (0.004, 0.024, and 0.008), IL‐6 (0.043), RANTES (0.033), IP‐10 (0.049), MCP‐1 (0.022), IL‐ 13 (0.029), and IL‐10 (0.026) than healthy controls when stimulated with various ligands. H3K4me3 expression was significantly lower in QFS patients than in healthy controls on the promoter regions of IL‐1β (p = 0.004), MCP‐1 (<0.001 and <0.001), IP‐10 (<0.001), IL‐10 (0.041), and IL‐13 (<0.001, <0.001, and 0.001). QFS patients showed diminished cytokine responses to various stimuli compared to age‐ and sex‐matched healthy controls, likely due to epigenetic remodeling and long‐term memory as a result from the acute Q fever infection. This might explain the upper respiratory tract ailments in QFS.     

A longitudinal study of psychological distress in women with breast symptoms

The aim of the study was to measure psychological distress in women with breast symptoms over a period of three months following an outpatient appointment at a rapid access symptomatic breast clinic. Women were recruited (N = 150) at the weekly clinic and psychological distress was measured using the Hospital Anxiety and Depression Scale, the General Health Questionnaire-12 and the Spielberger State-Trait Anxiety Inventory. Information on age and diagnosis was collected from medical notes. Measures were repeated at two weeks and at three months. Participants were divided into three diagnostic categories: B 1 (benign diagnosis at clinic); B2 (benign after further investigations); and M (breast cancer). Overall, scores of anxiety and GHQ-12 decreased significantly during the follow- up period. However, participants in the B2 group remained significantly more distressed than the rest of the sample throughout the experimental period. Depression remained within the normal range throughout the follow-up period for all categories. The study suggests a relationship between symptomatic breast disease and psychological distress.     

Abnormalities in cell-mediated immune functions to Haemophilus influenzae chronic purulent infections of the upper respiratory tract

Delayed hypersensitivity (dh) skin test reactivity to a somatic antigen of Haemophilus influenzae was studied in 21 patients with unexplained, chronically relapsing, purulent upper respiratory tract infections. Only 2 showed a dh reactivity comparable to that of healthy controls. A majority--15 patients--had a defective dh response, whereas 4 showed exaggerated reactivity leading to necrosis of the test site and general feelings of malaise. Not only was the dh reactivity to somatic H. influenzae antigen affected, but also that to streptokinase/streptodornase and candidal antigen in most cases, though to a lesser extent. Skin test reactivity to the mitogen PHA was normal as were the dh skin test reactivities in 4 out of 5 control patients with mucous atopic rhinitis/sinusitis and 2 cases of nasal suppuration due to disturbed mucociliary transport. Delayed hypersensitivity skin test disorders were associated with elevated ratios of OKT4 + /OKT8 + peripheral lymphoid cells. In addition a high incidence of atopy and thyroid autoimmunity was evident in patients as well as in their first-degree relatives. A negative lymphocyte proliferative response to somatic H. influenzae antigen was found in 3 of our patients. These results suggest that unexplained, chronically relapsing upper respiratory tract infections might be based on restricted T-cell defects to H. influenzae, streptococcal, and candidal antigens. Such defects are reminiscent of the T-cell immune disorders to fungi playing a role in some cases of chronic mucocutaneous candidiasis.     

A longitudinal cohort study of elderly women with urinary tract infections

AIMS: the prevalence of urinary tract infections (UTI), urinary incontinence (UI), estrogen-use and overall mortality in a cohort of elderly women who had been treated for UTI in 1985-86 was re-assessed 10 years later. MATERIAL AND METHODS: a random sample of 6000 women from the birth cohorts 1900, 1905, 1910, 1915 and 1920 were invited in 1986 to complete a questionnaire about UTI, UI and estrogen use (response rate 70%; n = 4206). Treatment with antibiotics for UTI during 1985-86 was reported by 688 (17%) women. In 1995 a similar questionnaire was sent to the women from this group who were still alive (n = 434). Mortality in the women with a history of UTI was compared with an aged-matched control group of women who did not have UTI during 1985-86. RESULTS: the questionnaire was completed and returned by 361 (83%) women. Treatment for at least one UTI during the last 9 years was reported by 219 (61%) women. The number of episodes varied: 35% had one to two UTI, 28% had three to four UTI, 27% five to ten UTI and 10% had had more than 10 UTI. In 1986, the prevalence of UI was higher in women with a history of UTI than in the total population sample (30 vs. 17%; P < 0.001). The prevalence of UI had increased from 30% in 1986 to 33% in 1995 (P < 0.05). Mortality in the women with a history of UTI was higher than in the aged-matched control group (37 vs. 28%; P < 0.001). A total of 162 (45%) women had received estrogen therapy at some time after the age of 60 years and 140 (39%) reported that they were currently taking low potency estrogens. CONCLUSION: elderly women with a history of UTI had a continued high occurrence of UTI and UI, and overall mortality was higher in these women than in an age-matched control group of women from the total population.     

Influenza and rhinovirus viral load and disease severity in upper respiratory tract infections

BackgroundThe role of viral load in respiratory viral infection is unclear. It is proposed that the viral load of some, but not all respiratory viruses correlate with disease severity.ObjectivesWe aimed to determine if an association exists between viral loads among patients in ambulatory settings, compared to those requiring hospitalization/intensive care unit (ICU) admission with influenza A/H3N2, influenza B, or human rhinovirus (HRV); we also explored the impact of age, gender and co-detection of Streptococcus pneumoniae on patient setting. We hypothesized that hospitalized/ICU patients have higher respiratory virus viral loads compared to ambulatory (e.g. walk-in clinics, family practices)/ER patients.Study designWe quantified viral load by in-house real-time RT-PCR in 774 nasopharyngeal swabs with influenza A/H3N2, or B or HRV viruses from various patient settings in Ontario, Canada.ResultsMean viral load (log₁₀ copies/ml) of influenza A/H3N2 (6.94) was higher than influenza B (4.96) and HRV (5.58) (p < 0.0001). Influenza A/H3N2 viral loads were highest in infants and the elderly; however, increased A/H3N2 viral loads were not associated with hospitalization/ICU admission compared to swabs collected in ambulatory/ER settings. Influenza B viral loads were higher in patients in hospital/ICU settings compared to those in ambulatory settings (OR 1.28, 95% CI 1.11–1.47). HRV viral loads did not differ by age (p = 0.67) or setting (p = 0.54); there was no association between S. pneumoniae colonization and setting for any virus.ConclusionWhen compared to ambulatory/ER patients, viral load was higher in hospitalized/ICU patients with influenza B, but not influenza A or HRV.     

Intravenous immunoglobulin replacement prevents severe and lower respiratory tract infections, but not upper respiratory tract and non-respiratory infections in common variable immune deficiency

BACKGROUND: Although the dose of 400 mg/kg body weight intravenous immunoglobulins (IVIG) every 3-4 weeks is now standard for treating patients with common variable immune deficiency, studies demonstrating its long-term benefits over low 200 mg/kg dose and its effects on infectious subsets (upper vs lower respiratory vs non-respiratory infections) are rare. METHODS: All patients from a single center with the diagnosis of common variable immune deficiency and whose clinical chart was available during three successive therapeutic periods [a pre-IVIG replacement period, a low-dose (200 mg/kg every 3 weeks) and a standard-dose replacement period (400 mg/kg every 3 weeks)] were screened retrospectively. RESULTS: Seven patients followed up for a total of 116 patient-years over the three defined periods of observation were recruited. When compared with low-dose therapy, standard-dose intravenous immunoglobulin therapy raised trough IgG levels from 4.3 to 6.5 g/l and significantly decreased the overall frequency of infections, with marked effects on lower respiratory tract and severe infection number. In contrast, non-respiratory and upper respiratory infections were, in comparison, resistant to therapy. CONCLUSIONS: Overall, these data support the use of standard-dose 400 mg/kg intravenous immunoglobulin therapy, despite the high cost, to raise trough IgG levels to 5-7 g/l, but underlines that some categories of infectious events (non-respiratory, upper respiratory) may need parallel surgical or pharmacological approaches to be optimally prevented or treated.     

Complex genetic and environmental relationships between psychological distress, fatigue and immune functioning: a twin study

BACKGROUND: Although there is considerable support for adverse relationships between states of psychological and somatic distress and immune response, there is little evidence in humans of the relative contribution of genetic and environmental factors. METHODS: This study utilized a twin methodology to examine the interplay between psychological distress, fatigue and immune function. We recorded a number of measures of distress, including conventional depression and anxiety as well as the somatic symptom of prolonged fatigue, and immune responsiveness (by delayed-type hypersensitivity skin response) in 124 normal adult twin pairs (79 monozygotic, 45 dizygotic). RESULTS: While there were strong genetic influences on the psychological distress and fatigue factors (only some of which are common to both), familial aggregation of immune responsiveness arose mainly from environmental factors shared by both members of a twin pair. Phenotypic correlations between psychological and immune measures were negligible, but multivariate genetic modelling revealed that these masked larger genetic and environmental correlations of opposite sign. Negative environmental effects of psychological distress and fatigue on immune responsiveness were countered by a positive genetic relationship between psychological distress and immune function. CONCLUSIONS: Our study suggests that current psychoneuroimmunological hypotheses in humans need to be modified to place increasing importance on the individual's genotype. In this cohort immune responsiveness varied in response to a complex interplay of genetic and environmental factors. Additionally, although psychological distress and fatigue had some shared genetic determinants, independent genetic and environmental risk factors for fatigue were also identified.     

A four year seasonal survey of the relationship between outdoor climate and epidemiology of viral respiratory tract infections in a temperate climate

BackgroundThe relation between weather conditions, viral transmission and seasonal activity of respiratory viruses is not fully understood.ObjectivesTo investigate the impact of outdoor weather in a temperate climate setting on the seasonal epidemiology of viruses causing respiratory tract infections, particularly influenza A (IFA).Study designIn total, 20,062 clinical nasopharyngeal swab samples referred for detection of respiratory pathogens using a multiplex PCR panel, between October 2010 and July 2013, were included. Results of PCR detection were compared with local meteorological data for the same period.ResultsLow temperature and vapor pressure (VP) were associated with weekly incidence of IFA, respiratory syncytial virus, metapneumovirus, bocavirus and adenovirus but no association with relative humidity was found. The incidence of human rhinovirus and enterovirus was independent of temperature. During seasonal IFA outbreaks, the weekly drop of average temperature (compared with the week before) was strongly associated with the IFA incidence recorded the following week.ConclusionA sudden drop in outdoor temperature might activate the annual influenza epidemic in a temperate climate by facilitating aerosol spread in dry air. These conditions also seem to affect the incidence of other respiratory pathogens but not human rhino- or enterovirus, suggesting that routes of infection other than aerosol may be relevant for these agents.     

Ultrastructural defects of respiratory tract cilia associated with chronic infections

Ultrastructural defects were demonstrated in nasal and bronchial cilia from a 12-year-old boy with repeated upper and lower respiratory tract infections. Numerous abnormalities were found, including single axonemes surrounded by excess cytoplasmic matrix, compound cilia, intracytoplasmic microtubular doublets, and cilia contained within a periciliary sheath. Dynein arms were missing from the majority of the peripheral microtubular doublets. The most striking abnormality, however, was a disorientation of cilia as judged by the increased variation in the orientation of central microtubules. Because of these ultrastructural abnormalities, it is highly likely that ciliary motility was markedly decreased and that defective mucociliary transport was responsible for chronic and repeated upper respiratory tract infections.     

A study on the role of noninvasive ventilation in mild-to-moderate acute respiratory distress syndrome

Aim:There is sparse data on the role of noninvasive ventilation (NIV) in acute respiratory distress syndrome (ARDS) from India. Herein, we report our experience with the use of NIV in mild to moderate ARDS.Results:A total of 41 subjects (27 women, mean age: 30.9 years) were included in the study. Tropical infections followed by abdominal sepsis were the most common causes of ARDS. The use of NIV was successful in 18 (44%) subjects, while 23 subjects required intubation. The median time to intubation was 3 h. Overall, 19 (46.3%) deaths were encountered, all in those requiring invasive ventilation. The mean duration of ventilation was significantly higher in the intubated patients (7.1 vs. 2.6 days, P = 0.004). Univariate analysis revealed a lack of improvement in PaO₂/FiO₂ at 1 h and high baseline Acute Physiology and Chronic Health Evaluation II (APACHE II) as predictors of NIV failure.Conclusions:Use of NIV in mild to moderate ARDS helped in avoiding intubation in about 44% of the subjects. A baseline APACHE II score of >17 and a PaO₂/FiO₂ ratio <150 at 1 h predicts NIV failure.