In patients with cystic fibrosis, inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function. This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease.

Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB. In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration). Further studies revealed that CS induced internalization of CFTR. Surprisingly, CS-internalized CFTR did not colocalize with lysosomal proteins. Instead, the bulk of CFTR shifted to a detergent-resistant fraction within the cell and colocalized with the intermediate filament vimentin, suggesting that CS induced CFTR movement into an aggresome-like, perinuclear compartment. To test whether airway dehydration could be reversed, we used hypertonic saline (HS) as an osmolyte to rehydrate ASL. HS restored ASL height in CS-exposed, dehydrated airway cultures. Similarly, inhaled HS restored mucus transport and increased clearance in patients with CB. Thus, we propose that CS exposure rapidly impairs CFTR function by internalizing CFTR, leading to ASL dehydration, which promotes mucus stasis and a failure of mucus clearance, leaving smokers at risk for developing CB. Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB.

Numerous epidemiologic studies have shown associations between exposure to particulate air pollution and acute increases in morbidity and mortality, particularly in persons with chronic obstructive pulmonary disease. The dosimetry of ultrafine particles in the human lung is poorly characterized. We studied the deposition and clearance of an ultrafine technetium-99m-labeled aerosol in 10 patients with chronic obstructive pulmonary disease and in 9 healthy subjects. Particle retention was followed for 2 hours after inhalation and again at 24 hours by gamma scintigraphy. Central-to-peripheral ratios indexed airway deposition. Particle accumulation in the liver was examined by quantifying activity below the right lung. The dose rate for an aerosol exposure of 10 micro g/m(3) was calculated. Patients had a significantly greater dose rate than healthy subjects (2.9 +/- 1.0 versus 1.9 +/- 0.4 micro g/h, p = 0.02). Central-to-peripheral ratios were slightly greater in patients than in healthy subjects (1.11 +/- 0.10 versus 1.01 +/- 0.11, p = 0.05). Clearance did not statistically differ between health and disease. On average, 24-hour retention was 85 +/- 8% (corrected for isotope dissolution). No accumulation in the liver's vicinity was observed. Data suggest that relative to healthy subjects, patients with moderate-to-severe airways obstruction receive an increased dose from ultrafine particle exposure.

Rationale: Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB.Objectives: We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance.Methods: We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB.Measurements and Results: CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV 1 , and both were significantly correlated.Conclusions: Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.

IMPORTANCEDuring the coronavirus disease 2019 (COVID-19) pandemic, the general public has been advised to wear masks or improvised face coverings to limit transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there has been considerable confusion and disagreement regarding the degree to which masks protect the wearer from airborne particles.OBJECTIVES To evaluate the fitted filtration efficiency (FFE) of various consumer-grade and improvised face masks, as well as several popular modifications of medical procedure masks that are intended to improve mask fit or comfort.DESIGN, SETTING, AND PARTICIPANTS For this study conducted in a research laboratory between June and August 2020, 7 consumer-grade masks and 5 medical procedure mask modifications were fitted on an adult male volunteer, and FFE measurements were collected during a series of repeated movements of the torso, head, and facial muscles as outlined by the US Occupational Safety and Health Administration Quantitative Fit Testing Protocol. The consumer-grade masks tested included (1) a 2-layer nylon mask with ear loops that was tested with an optional aluminum nose bridge and filter insert in place, (2) a cotton bandana folded diagonally once (ie, "bandit" style) or in a (3) multilayer rectangle according to the instructions presented by the US Surgeon General, (4) a single-layer polyester/nylon mask with ties, (5) a polypropylene mask with fixed ear loops, (6) a single-layer polyester gaiter/neck cover balaclava bandana, and (7) a 3-layer cotton mask with ear loops. Medical procedure mask modifications included (1) tying the mask's ear loops and tucking in the side pleats, (2) fastening ear loops behind the head with 3-dimensional-printed ear guards, (3) fastening ear loops behind the head with a claw-type hair clip, (4) enhancing the mask/face seal with rubber bands over the mask, and (5) enhancing the mask/face seal with a band of nylon hosiery over the fitted mask. MAIN OUTCOMES AND MEASURESThe primary study outcome was the measured FFE of common consumer-grade and improvised face masks, as well as several popular modifications of medical procedure masks. RESULTSThe mean (SD) FFE of consumer grade masks tested on 1 adult male with no beard ranged from 79.0% (4.3%) to 26.5% (10.5%), with the 2-layer nylon mask having the highest FFE. Unmodified medical procedure masks with ear loops had a mean (SD) FFE of 38.5% (11.2%). All modifications evaluated in this study increased procedure mask FFE (range [SD], 60.3% [11.1%] to 80.2% [3.1%]), with a nylon hosiery sleeve placed over the procedure mask producing the greatest improvement.CONCLUSIONS AND RELEVANCE While modifications to improve medical procedure mask fit can enhance the filtering capability and reduce inhalation of airborne particles, this study demonstrates that the FFEs of consumer-grade masks available to the public are, in many cases, nearly equivalent to or better than their non-N95 respirator medical mask counterparts.