Case Report: A Case of Wood-Smoke–Related Pulmonary Disease

CONTEXT: Biomass serves as a major fuel source for > 50% of the world’s population. The global burden of disease attributed to indoor air pollution from biomass combustion accounts for approximately 3% of worldwide disability-adjusted life-years lost. This is due to pneumonia in children and chronic obstructive pulmonary disease and lung cancer in women. CASE PRESENTATION: A 53-year-old man from Mexico was referred to the pulmonary clinic for evaluation of chronic productive cough and pulmonary nodules. In his youth, he worked at a charcoal plant in Mexico, where he burned wood and was exposed to massive amounts of smoke. His evaluation revealed thickened bronchovascular bundles with nodules on thoracic computed tomography, dark black plaques in large airways on bronchoscopy, and carbon-laden macrophages and fibrotic scars on lung biopsy. DISCUSSION: The patient was diagnosed with “hut lung,” a term that refers to the noninfectious, nonmalignant respiratory manifestations of chronic, high-level exposures to biomass smoke. This is the first reported case of hut lung associated with charcoal production. This case highlights that histopathologic abnormalities of the lung parenchyma may be present in patients with only mild symptoms and that clinical progression is likely a function of both the duration and intensity of exposure. RELEVANCE TO CLINICAL PRACTICE: As residents of lesser developed countries continue to be exposed to high levels of biomass smoke at work or at home and continue to immigrate to developed countries, it is important that health care providers in developed countries be aware of biomass-smoke–related pulmonary disease

Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection

BACKGROUND: Human β-defensin-4 (hBD-4), a new member of the β-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI) by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF). METHODS: The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA). Localization of hBD-4 was studied through immunohistochemical analysis (IHC). We investigated the effects of lipopolysaccharide (LPS) on hBD-4 expression and its release from small airway epithelial cells (SAEC). We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA. RESULTS: hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level. CONCLUSION: This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract

Tuberculosis and Indoor Biomass and Kerosene Use in Nepal: A Case–Control Study

BackgroundIn Nepal, tuberculosis (TB) is a major problem. Worldwide, six previous epidemiologic studies have investigated whether indoor cooking with biomass fuel such as wood or agricultural wastes is associated with TB with inconsistent results.ObjectivesUsing detailed information on potential confounders, we investigated the associations between TB and the use of biomass and kerosene fuels.MethodsA hospital-based case-control study was conducted in Pokhara, Nepal. Cases (n = 125) were women, 20-65 years old, with a confirmed diagnosis of TB. Age-matched controls (n = 250) were female patients without TB. Detailed exposure histories were collected with a standardized questionnaire.ResultsCompared with using a clean-burning fuel stove (liquefied petroleum gas, biogas), the adjusted odds ratio (OR) for using a biomass-fuel stove was 1.21 [95% confidence interval (CI), 0.48-3.05], whereas use of a kerosene-fuel stove had an OR of 3.36 (95% CI, 1.01-11.22). The OR for use of biomass fuel for heating was 3.45 (95% CI, 1.44-8.27) and for use of kerosene lamps for lighting was 9.43 (95% CI, 1.45-61.32).ConclusionsThis study provides evidence that the use of indoor biomass fuel, particularly as a source of heating, is associated with TB in women. It also provides the first evidence that using kerosene stoves and wick lamps is associated with TB. These associations require confirmation in other studies. If using kerosene lamps is a risk factor for TB, it would provide strong justification for promoting clean lighting sources, such as solar lamps

Extracellular DNA Chelates Cations and Induces Antibiotic Resistance in Pseudomonas aeruginosa Biofilms

Biofilms are surface-adhered bacterial communities encased in an extracellular matrix composed of DNA, bacterial polysaccharides and proteins, which are up to 1000-fold more antibiotic resistant than planktonic cultures. To date, extracellular DNA has been shown to function as a structural support to maintain Pseudomonas aeruginosa biofilm architecture. Here we show that DNA is a multifaceted component of P. aeruginosa biofilms. At physiologically relevant concentrations, extracellular DNA has antimicrobial activity, causing cell lysis by chelating cations that stabilize lipopolysaccharide (LPS) and the outer membrane (OM). DNA-mediated killing occurred within minutes, as a result of perturbation of both the outer and inner membrane (IM) and the release of cytoplasmic contents, including genomic DNA. Sub-inhibitory concentrations of DNA created a cation-limited environment that resulted in induction of the PhoPQ- and PmrAB-regulated cationic antimicrobial peptide resistance operon PA3552–PA3559 in P. aeruginosa. Furthermore, DNA-induced expression of this operon resulted in up to 2560-fold increased resistance to cationic antimicrobial peptides and 640-fold increased resistance to aminoglycosides, but had no effect on β-lactam and fluoroquinolone resistance. Thus, the presence of extracellular DNA in the biofilm matrix contributes to cation gradients, genomic DNA release and inducible antibiotic resistance. DNA-rich environments, including biofilms and other infection sites like the CF lung, are likely the in vivo environments where extracellular pathogens such as P. aeruginosa encounter cation limitation

Seasonal Patterns of Body Temperature Daily Rhythms in Group-Living Cape Ground Squirrels Xerus inauris

Organisms respond to cyclical environmental conditions by entraining their endogenous biological rhythms. Such physiological responses are expected to be substantial for species inhabiting arid environments which incur large variations in daily and seasonal ambient temperature (Ta). We measured core body temperature (Tb) daily rhythms of Cape ground squirrels Xerus inauris inhabiting an area of Kalahari grassland for six months from the Austral winter through to the summer. Squirrels inhabited two different areas: an exposed flood plain and a nearby wooded, shady area, and occurred in different social group sizes, defined by the number of individuals that shared a sleeping burrow. Of a suite of environmental variables measured, maximal daily Ta provided the greatest explanatory power for mean Tb whereas sunrise had greatest power for Tb acrophase. There were significant changes in mean Tb and Tb acrophase over time with mean Tb increasing and Tb acrophase becoming earlier as the season progressed. Squirrels also emerged from their burrows earlier and returned to them later over the measurement period. Greater increases in Tb, sometimes in excess of 5°C, were noted during the first hour post emergence, after which Tb remained relatively constant. This is consistent with observations that squirrels entered their burrows during the day to ‘offload’ heat. In addition, greater Tb amplitude values were noted in individuals inhabiting the flood plain compared with the woodland suggesting that squirrels dealt with increased environmental variability by attempting to reduce their Ta-Tb gradient. Finally, there were significant effects of age and group size on Tb with a lower and less variable Tb in younger individuals and those from larger group sizes. These data indicate that Cape ground squirrels have a labile Tb which is sensitive to a number of abiotic and biotic factors and which enables them to be active in a harsh and variable environment

The Ionizing Radiation-Induced Bystander Effect: Evidence, Mechanism, and Significance

It has long been considered that the important biological effects of ionizing radiation are a direct consequence of unrepaired or misrepaired DNA damage occurring in the irradiated cells. It was presumed that no effect would occur in cells in the population that receive no direct radiation exposure. However, in vitro evidence generated over the past two decades has indicated that non-targeted cells in irradiated cell cultures also experience significant biochemical and phenotypic changes that are often similar to those observed in the targeted cells. Further, nontargeted tissues in partial body-irradiated rodents also experienced stressful effects, including oxidative and oncogenic effects. This phenomenon, termed the “bystander response,” has been postulated to impact both the estimation of health risks of exposure to low doses/low fluences of ionizing radiation and the induction of second primary cancers following radiotherapy. Several mechanisms involving secreted soluble factors, oxidative metabolism, gap-junction intercellular communication, and DNA repair, have been proposed to regulate radiation-induced bystander effects. The latter mechanisms are major mediators of the system responses to ionizing radiation exposure, and our knowledge of the biochemical and molecular events involved in these processes is reviewed in this chapter